Comparison of excitation wavelengths for in vivo deep imaging of mouse brain

NASA Astrophysics Data System (ADS)

Wang, Mengran; Wu, Chunyan; Li, Bo; Xia, Fei; Sinefeld, David; Xu, Chris

2018-02-01

The attenuation of excitation power reaching the focus is the main issue that limits the depth penetration of highresolution imaging of biological tissue. The attenuation is caused by a combination of tissue scattering and absorption. Theoretical model of the effective attenuation length for in vivo mouse brain imaging has been built based on the data of the absorption of water and blood and the Mie scattering of a tissue-like phantom. Such a theoretical model has been corroborated at a number of excitation wavelengths, such as 800 nm, 1300 nm , and 1700 nm ; however, the attenuation caused by absorption is negligible when compared to tissue scattering at all these wavelength windows. Here we performed in vivo three-photon imaging of Texas Red-stained vasculature in the same mouse brain with different excitation wavelengths, 1700 nm, 1550 nm, 1500 nm and 1450 nm. In particular, our studies include the wavelength regime where strong water absorption is present (i.e., 1450 nm), and the attenuation by water absorption is predicted to be the dominant contribution in the excitation attenuation. Based on the experimental results, we found that the effective attenuation length at 1450 nm is significantly shorter than those at 1700 nm and 1300 nm. Our results confirm that the theoretical model based on tissue scattering and water absorption is accurate in predicting the effective attenuation lengths for in vivo imaging. The optimum excitation wavelength windows for in vivo mouse brain imaging are at 1300 nm and 1700 nm.

Photon Entanglement Through Brain Tissue.

PubMed

Shi, Lingyan; Galvez, Enrique J; Alfano, Robert R

2016-12-20

Photon entanglement, the cornerstone of quantum correlations, provides a level of coherence that is not present in classical correlations. Harnessing it by study of its passage through organic matter may offer new possibilities for medical diagnosis technique. In this work, we study the preservation of photon entanglement in polarization, created by spontaneous parametric down-conversion, after one entangled photon propagates through multiphoton-scattering brain tissue slices with different thickness. The Tangle-Entropy (TS) plots show the strong preservation of entanglement of photons propagating in brain tissue. By spatially filtering the ballistic scattering of an entangled photon, we find that its polarization entanglement is preserved and non-locally correlated with its twin in the TS plots. The degree of entanglement correlates better with structure and water content than with sample thickness.

Photon Entanglement Through Brain Tissue

NASA Astrophysics Data System (ADS)

Shi, Lingyan; Galvez, Enrique J.; Alfano, Robert R.

2016-12-01

Photon entanglement, the cornerstone of quantum correlations, provides a level of coherence that is not present in classical correlations. Harnessing it by study of its passage through organic matter may offer new possibilities for medical diagnosis technique. In this work, we study the preservation of photon entanglement in polarization, created by spontaneous parametric down-conversion, after one entangled photon propagates through multiphoton-scattering brain tissue slices with different thickness. The Tangle-Entropy (TS) plots show the strong preservation of entanglement of photons propagating in brain tissue. By spatially filtering the ballistic scattering of an entangled photon, we find that its polarization entanglement is preserved and non-locally correlated with its twin in the TS plots. The degree of entanglement correlates better with structure and water content than with sample thickness.

Photon Entanglement Through Brain Tissue

PubMed Central

Shi, Lingyan; Galvez, Enrique J.; Alfano, Robert R.

2016-01-01

Photon entanglement, the cornerstone of quantum correlations, provides a level of coherence that is not present in classical correlations. Harnessing it by study of its passage through organic matter may offer new possibilities for medical diagnosis technique. In this work, we study the preservation of photon entanglement in polarization, created by spontaneous parametric down-conversion, after one entangled photon propagates through multiphoton-scattering brain tissue slices with different thickness. The Tangle-Entropy (TS) plots show the strong preservation of entanglement of photons propagating in brain tissue. By spatially filtering the ballistic scattering of an entangled photon, we find that its polarization entanglement is preserved and non-locally correlated with its twin in the TS plots. The degree of entanglement correlates better with structure and water content than with sample thickness. PMID:27995952

Effects of tissue optical properties on time-resolved fluorescence measurements from brain tumors: an experimental and computational study

NASA Astrophysics Data System (ADS)

Butte, Pramod V.; Vishwanath, Karthik; Pikul, Brian K.; Mycek, Mary-Ann; Marcu, Laura

2003-07-01

Time-Resolved Laser-Induced Fluorescence Spectroscopy (tr-LIFS) offers the potential for intra-operative diagnosis of primary brain tumors. However, both the intrinsic properties of endogenous fluorophores and the optical properties of brain tissue could affect the fluorescence measurements from brain. Scattering has been demonstrated to increase, for instance, detected lifetimes by 10-20% in media less scattering than the brain. The overall goal of this study is to investigate experimentally and computationally how optical properties of distinct types of brain tissue (normal porcine white and gray matter) affect the propagation of the excitation pulse and fluorescent transients and the detected fluorescence lifetime. A time-domain tr-LIFS apparatus (fast digitizer and gated detection) was employed to measure the propagation of ultra-short pulsed light through brain specimens (1-2.5-mm source-detector separation; 0.100-mm increment). A Monte Carlo model for semi-infinite turbid media was used to simulate time-resolved light propagation for arbitrary source-detector fiber geometries and optical fiber specifications; and to record spatially- and temporally resolved information. We determined a good correlation between experimental and computational results. Our findings provide means for quantification of time-resolved fluorescence spectra from healthy and diseased brain tissue.

Confocal multispot microscope for fast and deep imaging in semicleared tissues

NASA Astrophysics Data System (ADS)

Adam, Marie-Pierre; Müllenbroich, Marie Caroline; Di Giovanna, Antonino Paolo; Alfieri, Domenico; Silvestri, Ludovico; Sacconi, Leonardo; Pavone, Francesco Saverio

2018-02-01

Although perfectly transparent specimens are imaged faster with light-sheet microscopy, less transparent samples are often imaged with two-photon microscopy leveraging its robustness to scattering; however, at the price of increased acquisition times. Clearing methods that are capable of rendering strongly scattering samples such as brain tissue perfectly transparent specimens are often complex, costly, and time intensive, even though for many applications a slightly lower level of tissue transparency is sufficient and easily achieved with simpler and faster methods. Here, we present a microscope type that has been geared toward the imaging of semicleared tissue by combining multispot two-photon excitation with rolling shutter wide-field detection to image deep and fast inside semicleared mouse brain. We present a theoretical and experimental evaluation of the point spread function and contrast as a function of shutter size. Finally, we demonstrate microscope performance in fixed brain slices by imaging dendritic spines up to 400-μm deep.

Quantitative analysis of transcranial and intraparenchymal light penetration in human cadaver brain tissue.

PubMed

Tedford, Clark E; DeLapp, Scott; Jacques, Steven; Anders, Juanita

2015-04-01

Photobiomodulation (PBM) also known as low-level light therapy has been used successfully for the treatment of injury and disease of the nervous system. The use of PBM to treat injury and diseases of the brain requires an in-depth understanding of light propagation through tissues including scalp, skull, meninges, and brain. This study investigated the light penetration gradients in the human cadaver brain using a Transcranial Laser System with a 30 mm diameter beam of 808 nm wavelength light. In addition, the wavelength-dependence of light scatter and absorbance in intraparenchymal brain tissue using 660, 808, and 940 nm wavelengths was investigated. Intact human cadaver heads (n = 8) were obtained for measurement of light propagation through the scalp/skull/meninges and into brain tissue. The cadaver heads were sectioned in either the transverse or mid-sagittal. The sectioned head was mounted into a cranial fixture with an 808 nm wavelength laser system illuminating the head from beneath with either pulsed-wave (PW) or continuous-wave (CW) laser light. A linear array of nine isotropic optical fibers on a 5 mm pitch was inserted into the brain tissue along the optical axis of the beam. Light collected from each fiber was delivered to a multichannel power meter. As the array was lowered into the tissue, the power from each probe was recorded at 5 mm increments until the inner aspect of the dura mater was reached. Intraparenchymal light penetration measurements were made by delivering a series of wavelengths (660, 808, and 940 nm) through a separate optical fiber within the array, which was offset from the array line by 5 mm. Local light penetration was determined and compared across the selected wavelengths. Unfixed cadaver brains provide good anatomical localization and reliable measurements of light scatter and penetration in the CNS tissues. Transcranial application of 808 nm wavelength light penetrated the scalp, skull, meninges, and brain to a depth of approximately 40 mm with an effective attenuation coefficient for the system of 2.22 cm(-1) . No differences were observed in the results between the PW and CW laser light. The intraparenchymal studies demonstrated less absorption and scattering for the 808 nm wavelength light compared to the 660 or 940 nm wavelengths. Transcranial light measurements of unfixed human cadaver brains allowed for determinations of light penetration variables. While unfixed human cadaver studies do not reflect all the conditions seen in the living condition, comparisons of light scatter and penetration and estimates of fluence levels can be used to establish further clinical dosing. The 808 nm wavelength light demonstrated superior CNS tissue penetration. © 2015 Wiley Periodicals, Inc.

Multiplex coherent anti-Stokes Raman scattering microspectroscopy of brain tissue with higher ranking data classification for biomedical imaging

NASA Astrophysics Data System (ADS)

Pohling, Christoph; Bocklitz, Thomas; Duarte, Alex S.; Emmanuello, Cinzia; Ishikawa, Mariana S.; Dietzeck, Benjamin; Buckup, Tiago; Uckermann, Ortrud; Schackert, Gabriele; Kirsch, Matthias; Schmitt, Michael; Popp, Jürgen; Motzkus, Marcus

2017-06-01

Multiplex coherent anti-Stokes Raman scattering (MCARS) microscopy was carried out to map a solid tumor in mouse brain tissue. The border between normal and tumor tissue was visualized using support vector machines (SVM) as a higher ranking type of data classification. Training data were collected separately in both tissue types, and the image contrast is based on class affiliation of the single spectra. Color coding in the image generated by SVM is then related to pathological information instead of single spectral intensities or spectral differences within the data set. The results show good agreement with the H&E stained reference and spontaneous Raman microscopy, proving the validity of the MCARS approach in combination with SVM.

Evans blue dye-enhanced imaging of the brain microvessels using spectral focusing coherent anti-Stokes Raman scattering microscopy

PubMed Central

Lee, Bo-Ram; Joo, Kyung-Il; Choi, Eun Sook; Jahng, Junghoon; Kim, Hyunmin

2017-01-01

We performed dye-enhanced imaging of mouse brain microvessels using spectral focusing coherent anti-Stokes Raman scattering (SF-CARS) microscopy. The resonant signals from C-H stretching in forward CARS usually show high background intensity in tissues, which makes CARS imaging of microvessels difficult. In this study, epi-detection of back-scattered SF-CARS signals showed a negligible background, but the overall intensity of resonant CARS signals was too low to observe the network of brain microvessels. Therefore, Evans blue (EB) dye was used as contrasting agent to enhance the back-scattered SF-CARS signals. Breakdown of brain microvessels by inducing hemorrhage in a mouse was clearly visualized using backward SF-CARS signals, following intravenous injection of EB. The improved visualization of brain microvessels with EB enhanced the sensitivity of SF-CARS, detecting not only the blood vessels themselves but their integrity as well in the brain vasculature. PMID:29049299

Non-destructive optical clearing technique enhances optical coherence tomography (OCT) for real-time, 3D histomorphometry of brain tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Paul, Akshay; Chang, Theodore H.; Chou, Li-Dek; Ramalingam, Tirunelveli S.

2016-03-01

Evaluation of neurodegenerative disease often requires examination of brain morphology. Volumetric analysis of brain regions and structures can be used to track developmental changes, progression of disease, and the presence of transgenic phenotypes. Current standards for microscopic investigation of brain morphology are limited to detection of superficial structures at a maximum depth of 300μm. While histological techniques can provide detailed cross-sections of brain structures, they require complicated tissue preparation and the ultimate destruction of the sample. A non-invasive, label-free imaging modality known as Optical Coherence Tomography (OCT) can produce 3-dimensional reconstructions through high-speed, cross-sectional scans of biological tissue. Although OCT allows for the preservation of intact samples, the highly scattering and absorbing properties of biological tissue limit imaging depth to 1-2mm. Optical clearing agents have been utilized to increase imaging depth by index matching and lipid digestion, however, these contemporary techniques are expensive and harsh on tissues, often irreversibly denaturing proteins. Here we present an ideal optical clearing agent that offers ease-of-use and reversibility. Similar to how SeeDB has been effective for microscopy, our fructose-based, reversible optical clearing technique provides improved OCT imaging and functional immunohistochemical mapping of disease. Fructose is a natural, non-toxic sugar with excellent water solubility, capable of increasing tissue transparency and reducing light scattering. We will demonstrate the improved depth-resolving performance of OCT for enhanced whole-brain imaging of normal and diseased murine brains following a fructose clearing treatment. This technique potentially enables rapid, 3-dimensional evaluation of biological tissues at axial and lateral resolutions comparable to histopathology.

Direct wavefront sensing for high-resolution in vivo imaging in scattering tissue

PubMed Central

Wang, Kai; Sun, Wenzhi; Richie, Christopher T.; Harvey, Brandon K.; Betzig, Eric; Ji, Na

2015-01-01

Adaptive optics by direct imaging of the wavefront distortions of a laser-induced guide star has long been used in astronomy, and more recently in microscopy to compensate for aberrations in transparent specimens. Here we extend this approach to tissues that strongly scatter visible light by exploiting the reduced scattering of near-infrared guide stars. The method enables in vivo two-photon morphological and functional imaging down to 700 μm inside the mouse brain. PMID:26073070

High-throughput isotropic mapping of whole mouse brain using multi-view light-sheet microscopy

NASA Astrophysics Data System (ADS)

Nie, Jun; Li, Yusha; Zhao, Fang; Ping, Junyu; Liu, Sa; Yu, Tingting; Zhu, Dan; Fei, Peng

2018-02-01

Light-sheet fluorescence microscopy (LSFM) uses an additional laser-sheet to illuminate selective planes of the sample, thereby enabling three-dimensional imaging at high spatial-temporal resolution. These advantages make LSFM a promising tool for high-quality brain visualization. However, even by the use of LSFM, the spatial resolution remains insufficient to resolve the neural structures across a mesoscale whole mouse brain in three dimensions. At the same time, the thick-tissue scattering prevents a clear observation from the deep of brain. Here we use multi-view LSFM strategy to solve this challenge, surpassing the resolution limit of standard light-sheet microscope under a large field-of-view (FOV). As demonstrated by the imaging of optically-cleared mouse brain labelled with thy1-GFP, we achieve a brain-wide, isotropic cellular resolution of 3μm. Besides the resolution enhancement, multi-view braining imaging can also recover complete signals from deep tissue scattering and attenuation. The identification of long distance neural projections across encephalic regions can be identified and annotated as a result.

Look-Ahead Distance of a fiber probe used to assist neurosurgery: Phantom and Monte Carlo study

NASA Astrophysics Data System (ADS)

Qian, Zhiyu; Victor, Sunder S.; Gu, Yueqing; Giller, Cole A.; Liu, Hanli

2003-08-01

A short-separation, optical reflectance probe has been developed to assist the neurosurgeon in functional neurosurgery for accurate localization of the surgical target. Because of the scattering nature of tissue, the optical probe has a "Look Ahead Distance" (LAD), at which the measured optical reflectance starts to "see" or "sense" the underlying brain structure due to the difference in light scattering of tissue. To quantify the LAD, 2-layer laboratory phantoms have been developed to mimic gray and white matter of the brain, and Monte Carlo simulations have been also used to confirm the experimental findings. Based on both the laboratory and simulation results, a quantitative empirical equation is developed to express the LAD as a function of scattering coefficient of the measured tissue for a 400-micron-diameter fiber probe. The quantified LAD of the probe is highly desirable so as to improve the spatial resolution of the probe for better surgery guidance.

In vivo optoacoustic monitoring of calcium activity in the brain (Conference Presentation)

NASA Astrophysics Data System (ADS)

Deán-Ben, Xose Luís.; Gottschalk, Sven; Sela, Gali; Lauri, Antonella; Kneipp, Moritz; Ntziachristos, Vasilis; Westmeyer, Gil G.; Shoham, Shy; Razansky, Daniel

2017-03-01

Non-invasive observation of spatio-temporal neural activity of large neural populations distributed over the entire brain of complex organisms is a longstanding goal of neuroscience [1,2]. Recently, genetically encoded calcium indicators (GECIs) have revolutionized neuroimaging by enabling mapping the activity of entire neuronal populations in vivo [3]. Visualization of these powerful sensors with fluorescence microscopy has however been limited to superficial regions while deep brain areas have so far remained unreachable [4]. We have developed a volumetric multispectral optoacoustic tomography platform for imaging neural activation deep in scattering brains [5]. The developed methodology can render 100 volumetric frames per second across scalable fields of view ranging between 50-1000 mm3 with respective spatial resolution of 35-150µm. Experiments performed in immobilized and freely swimming larvae and in adult zebrafish brains expressing the genetically-encoded calcium indicator GCaMP5G demonstrated, for the first time, the fundamental ability to directly track neural dynamics using optoacoustics while overcoming the depth barrier of optical imaging in scattering brains [6]. It was further possible to monitor calcium transients in a scattering brain of a living adult transgenic zebrafish expressing GCaMP5G calcium indicator [7]. Fast changes in optoacoustic traces associated to GCaMP5G activity were detectable in the presence of other strongly absorbing endogenous chromophores, such as hemoglobin. The results indicate that the optoacoustic signal traces generally follow the GCaMP5G fluorescence dynamics and further enable overcoming the longstanding optical-diffusion penetration barrier associated to scattering in biological tissues [6]. The new functional optoacoustic neuroimaging method can visualize neural activity at penetration depths and spatio-temporal resolution scales not covered with the existing neuroimaging techniques. Thus, in addition to the well-established capacity of optoacoustics to resolve vascular anatomy and multiple hemodynamic parameters deep in scattering tissues, the newly developed methodology offers unprecedented capabilities for functional whole brain observations of fast calcium dynamics.

Levels of detail analysis of microwave scattering from human head models for brain stroke detection

PubMed Central

2017-01-01

In this paper, we have presented a microwave scattering analysis from multiple human head models. This study incorporates different levels of detail in the human head models and its effect on microwave scattering phenomenon. Two levels of detail are taken into account; (i) Simplified ellipse shaped head model (ii) Anatomically realistic head model, implemented using 2-D geometry. In addition, heterogenic and frequency-dispersive behavior of the brain tissues has also been incorporated in our head models. It is identified during this study that the microwave scattering phenomenon changes significantly once the complexity of head model is increased by incorporating more details using magnetic resonance imaging database. It is also found out that the microwave scattering results match in both types of head model (i.e., geometrically simple and anatomically realistic), once the measurements are made in the structurally simplified regions. However, the results diverge considerably in the complex areas of brain due to the arbitrary shape interface of tissue layers in the anatomically realistic head model. After incorporating various levels of detail, the solution of subject microwave scattering problem and the measurement of transmitted and backscattered signals were obtained using finite element method. Mesh convergence analysis was also performed to achieve error free results with a minimum number of mesh elements and a lesser degree of freedom in the fast computational time. The results were promising and the E-Field values converged for both simple and complex geometrical models. However, the E-Field difference between both types of head model at the same reference point differentiated a lot in terms of magnitude. At complex location, a high difference value of 0.04236 V/m was measured compared to the simple location, where it turned out to be 0.00197 V/m. This study also contributes to provide a comparison analysis between the direct and iterative solvers so as to find out the solution of subject microwave scattering problem in a minimum computational time along with memory resources requirement. It is seen from this study that the microwave imaging may effectively be utilized for the detection, localization and differentiation of different types of brain stroke. The simulation results verified that the microwave imaging can be efficiently exploited to study the significant contrast between electric field values of the normal and abnormal brain tissues for the investigation of brain anomalies. In the end, a specific absorption rate analysis was carried out to compare the ionizing effects of microwave signals to different types of head model using a factor of safety for brain tissues. It is also suggested after careful study of various inversion methods in practice for microwave head imaging, that the contrast source inversion method may be more suitable and computationally efficient for such problems. PMID:29177115

Profound and Sexually Dimorphic Effects of Clinically-Relevant Low Dose Scatter Irradiation on the Brain and Behavior

PubMed Central

Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Yaroslav; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kolb, Bryan; Kovalchuk, Olga

2016-01-01

Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders). While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way. PMID:27375442

Bayesian estimation of optical properties of the human head via 3D structural MRI

NASA Astrophysics Data System (ADS)

Barnett, Alexander H.; Culver, Joseph P.; Sorensen, A. Gregory; Dale, Anders M.; Boas, David A.

2003-10-01

Knowledge of the baseline optical properties of the tissues of the human head is essential for absolute cerebral oximetry, and for quantitative studies of brain activation. In this work we numerically model the utility of signals from a small 6-optode time-resolved diffuse optical tomographic apparatus for inferring baseline scattering and absorption coefficients of the scalp, skull and brain, when complete geometric information is available from magnetic resonance imaging (MRI). We use an optical model where MRI-segmented tissues are assumed homogeneous. We introduce a noise model capturing both photon shot noise and forward model numerical accuracy, and use Bayesian inference to predict errorbars and correlations on the measurments. We also sample from the full posterior distribution using Markov chain Monte Carlo. We conclude that ~ 106 detected photons are sufficient to measure the brain"s scattering and absorption to a few percent. We present preliminary results using a fast multi-layer slab model, comparing the case when layer thicknesses are known versus unknown.

Bioorthogonal chemical imaging of metabolic activities in live mammalian hippocampal tissues with stimulated Raman scattering

NASA Astrophysics Data System (ADS)

Hu, Fanghao; Lamprecht, Michael R.; Wei, Lu; Morrison, Barclay; Min, Wei

2016-12-01

Brain is an immensely complex system displaying dynamic and heterogeneous metabolic activities. Visualizing cellular metabolism of nucleic acids, proteins, and lipids in brain with chemical specificity has been a long-standing challenge. Recent development in metabolic labeling of small biomolecules allows the study of these metabolisms at the global level. However, these techniques generally require nonphysiological sample preparation for either destructive mass spectrometry imaging or secondary labeling with relatively bulky fluorescent labels. In this study, we have demonstrated bioorthogonal chemical imaging of DNA, RNA, protein and lipid metabolism in live rat brain hippocampal tissues by coupling stimulated Raman scattering microscopy with integrated deuterium and alkyne labeling. Heterogeneous metabolic incorporations for different molecular species and neurogenesis with newly-incorporated DNA were observed in the dentate gyrus of hippocampus at the single cell level. We further applied this platform to study metabolic responses to traumatic brain injury in hippocampal slice cultures, and observed marked upregulation of protein and lipid metabolism particularly in the hilus region of the hippocampus within days of mechanical injury. Thus, our method paves the way for the study of complex metabolic profiles in live brain tissue under both physiological and pathological conditions with single-cell resolution and minimal perturbation.

TU-F-CAMPUS-T-02: Risk Assessment of Scattered Neutrons for a Fetus From Proton Therapy of a Brain Tumor During Pregnancy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, C; Nanjing University of Aeronautics and Astronautics, Nanjing; Moteabbed, M

Purpose: To determine the scattered neutron dose and the resulting risk for a fetus from proton therapy for brain tumors during pregnancy. Methods: Using the Monte Carlo platform TOPAS, the ICRP reference parameters based anthropomorphic pregnancy phantoms for three stages (3-, 6-, 9-month) were applied to evaluate the scattered neutron dose and dose equivalent. To calculate the dose equivalent, organ specific linear energy transfer (LET) based quality factor was used. Treatment plans from both passive scattering (PS) and pencil beam scanning (PBS) methods were considered in this study. Results: For pencil beam scanning, the neutron dose equivalent in the softmore » tissue of the fetus increases from 1.53x10−{sup 3} to 2.84x10−{sup 3} mSv per treatment Gy with increasing stage of gestation. This is due to scattered neutrons from the patient as the main contaminant source in PBS and a decrease in distance between the soft tissue of the fetus and GTV with increasing stage of gestation. For passive scattering, neutron dose equivalent to the soft tissue of the fetus shows a decrease from 0.17 to 0.13 mSv per treatment Gy in different stages, while the dose to the brain shows little difference around 0.18 mSv per treatment Gy because scattered neutrons from the treatment head contribute predominantly in passive scattering. Conclusion: The results show that the neutron dose to the fetus assuming a prescribed dose of 52.2 Gy is negligible for PBS, and is comparable to the scattered dose (0–10 mSv) from a head and neck CT scan for PS. It can be concluded that the dose to fetus is far lower than the thresholds of malformation, SMR and lethal death. The excess relative risk of childhood cancer induction would be increased by 0.48 and 0.103 using the Oxford Survey of Childhood Cancers and Japanese atomic model, respectively. Changran Geng is supported by the Chinese Scholarship Council (CSC) and the National Natural Science Foundation of China (Grant No. 11475087)« less

Wavelet-domain de-noising of OCT images of human brain malignant glioma

NASA Astrophysics Data System (ADS)

Dolganova, I. N.; Aleksandrova, P. V.; Beshplav, S.-I. T.; Chernomyrdin, N. V.; Dubyanskaya, E. N.; Goryaynov, S. A.; Kurlov, V. N.; Reshetov, I. V.; Potapov, A. A.; Tuchin, V. V.; Zaytsev, K. I.

2018-04-01

We have proposed a wavelet-domain de-noising technique for imaging of human brain malignant glioma by optical coherence tomography (OCT). It implies OCT image decomposition using the direct fast wavelet transform, thresholding of the obtained wavelet spectrum and further inverse fast wavelet transform for image reconstruction. By selecting both wavelet basis and thresholding procedure, we have found an optimal wavelet filter, which application improves differentiation of the considered brain tissue classes - i.e. malignant glioma and normal/intact tissue. Namely, it allows reducing the scattering noise in the OCT images and retaining signal decrement for each tissue class. Therefore, the observed results reveals the wavelet-domain de-noising as a prospective tool for improved characterization of biological tissue using the OCT.

Measuring aberrations in the rat brain by coherence-gated wavefront sensing using a Linnik interferometer

PubMed Central

Wang, Jinyu; Léger, Jean-François; Binding, Jonas; Boccara, A. Claude; Gigan, Sylvain; Bourdieu, Laurent

2012-01-01

Aberrations limit the resolution, signal intensity and achievable imaging depth in microscopy. Coherence-gated wavefront sensing (CGWS) allows the fast measurement of aberrations in scattering samples and therefore the implementation of adaptive corrections. However, CGWS has been demonstrated so far only in weakly scattering samples. We designed a new CGWS scheme based on a Linnik interferometer and a SLED light source, which is able to compensate dispersion automatically and can be implemented on any microscope. In the highly scattering rat brain tissue, where multiply scattered photons falling within the temporal gate of the CGWS can no longer be neglected, we have measured known defocus and spherical aberrations up to a depth of 400 µm. PMID:23082292

Measuring aberrations in the rat brain by coherence-gated wavefront sensing using a Linnik interferometer.

PubMed

Wang, Jinyu; Léger, Jean-François; Binding, Jonas; Boccara, A Claude; Gigan, Sylvain; Bourdieu, Laurent

2012-10-01

Aberrations limit the resolution, signal intensity and achievable imaging depth in microscopy. Coherence-gated wavefront sensing (CGWS) allows the fast measurement of aberrations in scattering samples and therefore the implementation of adaptive corrections. However, CGWS has been demonstrated so far only in weakly scattering samples. We designed a new CGWS scheme based on a Linnik interferometer and a SLED light source, which is able to compensate dispersion automatically and can be implemented on any microscope. In the highly scattering rat brain tissue, where multiply scattered photons falling within the temporal gate of the CGWS can no longer be neglected, we have measured known defocus and spherical aberrations up to a depth of 400 µm.

Photon dynamics in tissue imaging

NASA Astrophysics Data System (ADS)

Chance, Britton; Haselgrove, John C.; Wang, NaiGuang; Maris, Michael B.; Sevick-Muraca, Eva M.

1991-11-01

The emerging need for a fast, safe economical approach to global and localized measures of desaturation of hemoglobin with oxygen (HbO2) in the human brain motivates further research on time-resolved spectroscopy in four areas of study. (1) To afford quantization of hemoglobin saturation through time-resolved spectroscopy in the time domain (TD) and in the frequency domain (FD). Evaluation of dual-wavelength TD and FD spectrometers for determining quantitatively hemoglobin desaturation and blood-volume changes by calculations that are insensitive to mutual interference is proposed. The diffusion equation, as it applies especially to TD studies, and the absorption ((mu) a) and scattering ((mu) s) coefficients provide their independent determination from the late and early respective portions of the kinetics of the emergent photons in response to a short input pulse (50-100 psec). (2) The identification of the photon-pathlength change due to the arterial pulse in the brain tissue by FD methods with Fourier transformation affords an opportunity to employ principles of pulse oximetry to vessels localized deep within the brain tissue. (3) Localization of desaturation of hemoglobin in portions of the brain can be achieved through dual-wavelength scanning of the input/output optical fibers across the head for an X-Y coordinate and varying the distance between input and output ((rho) ) or the time delay in data acquisition to afford an in-depth Z scan. Localizations of shed blood, which have an effective concentration of over 10 times that of capillary-bed blood, are identified by X, Y, Z scans using only a single wavelength. (4) Independent measurements of absorption ((mu) a) and scattering ((mu) s) coefficients, particularly by TD techniques, affords structural mapping of the brain, which can be used to diagnose brain tumor and neuronal degeneration. Two experimental systems are used to critically evaluate these studies; the first, a hemoglobin/lipid/yeast model in which intermittent oxygenation gives saturation/desaturation effects and addition of hemoglobin simulates increased blood volume. These models can be global or may contain localized ''black'' absorbers simulating brain bleeds or model-stroke volumes in which oxygenation/deoxygenation simulates normoxia/hypoxia. Secondly, animal brains are used to model the following changes in vivo: global or localized hypoxia, brain bleeding, and hematomas by epidural blood injection, and physiological changes by epilepsy. Neuronal degeneration causing scattering effects is modeled by injection, epidurally or into the animal model brain, highly scattering material such as polystyrene spheres. The proposal envisages a basic science study of photon migration in the brain with important applications to stroke, epilepsy, brain trauma, and neuronal degenerative disease.

TU-D-209-06: Head and Neck Tissue Dose From X-Ray Scatter to Physicians Performing Cardiovascular Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fetterly, K; Schueler, B; Grams, M

Purpose: The purpose of this work was to characterize the spatial distribution of scatter radiation to the head and neck of a physician performing an x-ray interventional procedure and assess brain, eye lens, and carotid artery dose. Methods: Radiographic x-ray beams were tuned to match the peak energy (56 to 106 keV) and HVL (3.5 to 6.5 mm Al) of x-ray scatter originating from a patient during a fluoroscopic procedure. The radiographic beam was directed upon a Rando phantom from an inferior-left location to mimic a typical patient-operator geometric relationship. A lead-equivalent protective garment was secured to the phantom. Directmore » exposure Gafchromic film (XRQA2) was placed between the transverse plane layers of the head and neck region of the phantom and exposed with 4 scatter-equivalent radiographic beams. A 3×3 cm{sup 2} film placed at the left collar of the phantom was used to monitor incident dose in the position of a radiation monitoring badge. The films were converted to 2D dose distribution maps using FilmQA Pro software and an Epson 11000-XL scanner. The 2D dose distributions maps were normalized by the left collar dose and the percent of left collar dose (%LCD) was calculated for select tissues. Results: The dose maps had high dynamic range (10{sub 4}) and spatial detail. Considering all transverse planes and 4 scatter beam qualities, the median %LCD values were: whole brain 8.5%, left brain 13%, right brain 5.4%, left eye lens 67%, right eye lens 25%, left carotid artery 72%, and right carotid artery 28%. Conclusion: Scatter radiation dose to an operator can be simulated using a tuned radiographic beam and used to expose a phantom and Gafchromic film, thereby creating detailed 2D dose distribution maps. This work facilitates individualized estimation of dose to select head and neck tissues based on an operator’s radiation monitoring badge value.« less

Laser scattering by transcranial rat brain illumination

NASA Astrophysics Data System (ADS)

Sousa, Marcelo V. P.; Prates, Renato; Kato, Ilka T.; Sabino, Caetano P.; Suzuki, Luis C.; Ribeiro, Martha S.; Yoshimura, Elisabeth M.

2012-06-01

Due to the great number of applications of Low-Level-Laser-Therapy (LLLT) in Central Nervous System (CNS), the study of light penetration through skull and distribution in the brain becomes extremely important. The aim is to analyze the possibility of precise illumination of deep regions of the rat brain, measure the penetration and distribution of red (λ = 660 nm) and Near Infra-Red (NIR) (λ = 808 nm) diode laser light and compare optical properties of brain structures. The head of the animal (Rattus Novergicus) was epilated and divided by a sagittal cut, 2.3 mm away from mid plane. This section of rat's head was illuminated with red and NIR lasers in points above three anatomical structures: hippocampus, cerebellum and frontal cortex. A high resolution camera, perpendicularly positioned, was used to obtain images of the brain structures. Profiles of scattered intensities in the laser direction were obtained from the images. There is a peak in the scattered light profile corresponding to the skin layer. The bone layer gives rise to a valley in the profile indicating low scattering coefficient, or frontal scattering. Another peak in the region related to the brain is an indication of high scattering coefficient (μs) for this tissue. This work corroborates the use of transcranial LLLT in studies with rats which are subjected to models of CNS diseases. The outcomes of this study point to the possibility of transcranial LLLT in humans for a large number of diseases.

Near-infrared diffuse reflectance imaging of infarct core and peri-infarct depolarization in a rat middle cerebral artery occlusion model

NASA Astrophysics Data System (ADS)

Kawauchi, Satoko; Nishidate, Izumi; Nawashiro, Hiroshi; Sato, Shunichi

2014-03-01

To understand the pathophysiology of ischemic stroke, in vivo imaging of the brain tissue viability and related spreading depolarization is crucial. In the infarct core, impairment of energy metabolism causes anoxic depolarization (AD), which considerably increases energy consumption, accelerating irreversible neuronal damage. In the peri-infarct penumbra region, where tissue is still reversible despite limited blood flow, peri-infarct depolarization (PID) occurs, exacerbating energy deficit and hence expanding the infarct area. We previously showed that light-scattering signal, which is sensitive to cellular/subcellular structural integrity, was correlated with AD and brain tissue viability in a rat hypoxia-reoxygenation model. In the present study, we performed transcranial NIR diffuse reflectance imaging of the rat brain during middle cerebral artery (MCA) occlusion and examined whether the infarct core and PIDs can be detected. Immediately after occluding the left MCA, light scattering started to increase focally in the occlusion site and a bright region was generated near the occlusion site and spread over the left entire cortex, which was followed by a dark region, showing the occurrence of PID. The PID was generated repetitively and the number of times of occurrence in a rat ranged from four to ten within 1 hour after occlusion (n=4). The scattering increase in the occlusion site was irreversible and the area with increased scattering expanded with increasing the number of PIDs, indicating an expansion of the infarct core. These results suggest the usefulness of NIR diffuse reflectance signal to visualize spatiotemporal changes in the infarct area and PIDs.

Feasibility of in Vivo SAXS Imaging for Detection of Alzheiemer's Disease

NASA Astrophysics Data System (ADS)

Choi, Mina

Small-angle x-ray scattering (SAXS) imaging has been proposed as a technique to characterize and selectively image structures based on electron density structure which allows for discriminating materials based on their scatter cross sections. This dissertation explores the feasibility of SAXS imaging for the detection of Alzheimer's disease (AD) amyloid plaques. The inherent scatter cross sections of amyloid plaque serve as biomarkers in vivo without the need of injected molecular tags. SAXS imaging can also assist in a better understanding of how these biomarkers play a role in Alzheimer's disease which in turn can lead to the development of more effective disease-modifying therapies. I implement simulations of x-ray transport using Monte Carlo methods for SAXS imaging enabling accurate calculation of radiation dose and image quality in SAXS-computed tomography (CT). I describe SAXS imaging phantoms with tissue-mimicking material and embedded scatter targets as a way of demonstrating the characteristics of SAXS imaging. I also performed a comprehensive study of scattering cross sections of brain tissue from measurements of ex-vivo sections of a wild-type mouse brain and reported generalized cross sections of gray matter, white matter, and corpus callosum obtained and registered by planar SAXS imaging. Finally, I demonstrate the ability of SAXS imaging to locate an amyloid fibril pellet within a brain section. This work contributes to novel application of SAXS imaging for Alzheimer's disease detection and studies its feasibility as an imaging tool for AD biomarkers.

Interpreting CARS images of tissue within the C-H-stretching region

NASA Astrophysics Data System (ADS)

Dietzek, Benjamin; Meyer, Tobias; Medyukhina, Anna; Bergner, Norbert; Krafft, Christoph; Romeike, Bernd F. M.; Reichart, Rupert; Kalff, Rolf; Schmitt, Michael; Popp, Jürgen

2014-03-01

Single band coherent anti-Stokes Raman scattering (CARS) microscopy within the CH-stretching region is applied to detect individual cells and nuclei of human brain tissue and brain tumors - an information which allows for histopathologic grading of the tissue. The CARS image contrast within the C-H-stretching region correlated to the tissue composition. Based on the specific application example of identifying nuclei within (coherent) Raman images of neurotissue sections, we shall derive general design parameters for lasers optimally suited to serve in a clinical environment and discuss the potential of recently developed methods to analyze spectrally resolved CARS images and image segmentation algorithms.

Determination of fluence rate and temperature distributions in the rat brain; implications for photodynamic therapy.

PubMed

Angell-Petersen, Even; Hirschberg, Henry; Madsen, Steen J

2007-01-01

Light and heat distributions are measured in a rat glioma model used in photodynamic therapy. A fiber delivering 632-nm light is fixed in the brain of anesthetized BDIX rats. Fluence rates are measured using calibrated isotropic probes that are positioned stereotactically. Mathematical models are then used to derive tissue optical properties, enabling calculation of fluence rate distributions for general tumor and light application geometries. The fluence rates in tumor-free brains agree well with the models based on diffusion theory and Monte Carlo simulation. In both cases, the best fit is found for absorption and reduced scattering coefficients of 0.57 and 28 cm(-1), respectively. In brains with implanted BT(4)C tumors, a discrepancy between diffusion and Monte Carlo-derived two-layer models is noted. Both models suggest that tumor tissue has higher absorption and less scattering than normal brain. Temperatures are measured by inserting thermocouples directly into tumor-free brains. A model based on diffusion theory and the bioheat equation is found to be in good agreement with the experimental data and predict a thermal penetration depth of 0.60 cm in normal rat brain. The predicted parameters can be used to estimate the fluences, fluence rates, and temperatures achieved during photodynamic therapy.

The relationship between decorrelation time and sample thickness in acute rat brain tissue slices (Conference Presentation)

NASA Astrophysics Data System (ADS)

Brake, Joshua; Jang, Mooseok; Yang, Changhuei

2016-03-01

The optical opacity of biological tissue has long been a challenge in biomedical optics due to the strong scattering nature of tissue in the optical regime. While most conventional optical techniques attempt to gate out multiply scattered light and use only unscattered light, new approaches in the field of wavefront shaping exploit the time reversible symmetry of optical scattering in order to focus light inside or through scattering media. While these approaches have been demonstrated effectively on static samples, it has proven difficult to apply them to dynamic biological samples since even small changes in the relative positions of the scatterers within will cause the time symmetry that wavefront shaping relies upon to decorrelate. In this paper we investigate the decorrelation curves of acute rat brain slices for thicknesses in the range 1-3 mm (1/e decorrelation time on the order of seconds) using multi-speckle diffusing wave spectroscopy (MSDWS) and compare the results with theoretical predictions. The results of this study demonstrate that the 1/L^2 relationship between decorrelation time and thickness predicted by diffusing wave spectroscopy provides a good rule of thumb for estimating how the decorrelation of a sample will change with increasing thickness. Understanding this relationship will provide insight to guide the future development of biophotonic wavefront shaping tools by giving an estimate of how fast wavefront shaping systems need to operate to overcome the dynamic nature of biological samples.

Near-infrared spectroscopy technique to evaluate the effects of drugs in treating traumatic brain edema

NASA Astrophysics Data System (ADS)

Xie, J.; Qian, Z.; Yang, T.; Li, W.; Hu, G.

2011-01-01

The aim of this study was to evaluate the effects of several drugs in treating traumatic brain edema (TBE) following traumatic brain injury (TBI) using near-infrared spectroscopy (NIRs) technology. Rats with TBE models were given hypertonic saline (HS), mannitol and mannitol+HS respectively for different groups. Light scattering properties of rat's local cortex was measured by NIRs within the wavelength range from 700 to 850 nm. TBE models were built in rats' left brains. The scattering properties of the right and left target corresponding to the position of normal and TBE tissue were measured and recorded in vivo and real-time by a bifurcated needle probe. The brain water contents (BWC) were measured by the wet and dry weight method after injury and treatment hours 1, 6, 24, 72 and 120. A marked linear relationship was observed between reduced scattering coefficient (μs') and BWC. By recording μs' of rats' brains, the entire progressions of effects of several drugs were observed. The result may suggest that the NIRs techniques have a potential for assessing effects in vivo and real-time on treatment of the brain injury.

Optical imaging characterizing brain response to thermal insult in injured rodent

NASA Astrophysics Data System (ADS)

Abookasis, David; Shaul, Oren; Meitav, Omri; Pinhasi, Gadi A.

2018-02-01

We used spatially modulated optical imaging system to assess the effect of temperature elevation on intact brain tissue in a mouse heatstress model. Heatstress or heatstroke is a medical emergency defined by abnormally elevated body temperature that causes biochemical, physiological and hematological changes. During experiments, brain temperature was measured concurrently with a thermal camera while core body temperature was monitored with rectal thermocouple probe. Changes in a battery of macroscopic brain physiological parameters, such as hemoglobin oxygen saturation level, cerebral water content, as well as intrinsic tissue optical properties were monitored during temperature elevation. These concurrent changes reflect the pathophysiology of the brain during heatstress and demonstrate successful monitoring of thermoregulation mechanisms. In addition, the variation of tissue refractive index was calculated showing a monotonous decrease with increasing wavelength. We found increased temperature to greatly affect both the scattering properties and refractive index which represent cellular and subcellular swelling indicative of neuronal damage. The overall trends detected in brain tissue parameters were consistent with previous observations using conventional medical devices and optical modalities.

Near Infrared Light Scattering Changes Following Acute Brain Injury

PubMed Central

Highton, David; Tachtsidis, Ilias; Tucker, Alison; Elwell, Clare; Smith, Martin

2018-01-01

Acute brain injury (ABI) is associated with changes in near infrared light absorption reflecting haemodynamic and metabolic status via changes in cerebral oxygenation (haemoglobin oxygenation and cytochrome-c-oxidase oxidation). Light scattering has not been comprehensively investigated following ABI and may be an important confounding factor in the assessment of chromophore concentration changes, and/or a novel non-invasive optical marker of brain tissue morphology, cytostructure, hence metabolic status. The aim of this study is to characterize light scattering following adult ABI. Time resolved spectroscopy was performed as a component of multimodal neuromonitoring in critically ill brain injured patients. The scattering coefficient (μ′s), absorption coefficient and cerebral haemoglobin oxygen saturation (SO2) were derived by fitting the time resolved data. Cerebral infarction was subsequently defined on routine clinical imaging. In total, 21 patients with ABI were studied. Ten patients suffered a unilateral frontal infarction, and mean μ′s was lower over infarcted compared to non-infarcted cortex (injured 6.9/cm, non-injured 8.2/cm p = 0.002). SO2 did not differ significantly between the two sides (injured 69.3 %, non-injured 69.0 % p = 0.7). Cerebral infarction is associated with changes in μ′s which might be a novel marker of cerebral injury and will interfere with quantification of haemoglobin/cytochrome c oxidase concentration. Although further work combining optical and physiological analysis is required to elucidate the significance of these results, μ′s may be uniquely placed as a non-invasive biomarker of cerebral energy failure as well as gross tissue changes. PMID:26782205

Label-free volumetric optical imaging of intact murine brains

NASA Astrophysics Data System (ADS)

Ren, Jian; Choi, Heejin; Chung, Kwanghun; Bouma, Brett E.

2017-04-01

A central effort of today’s neuroscience is to study the brain’s ’wiring diagram’. The nervous system is believed to be a network of neurons interacting with each other through synaptic connection between axons and dendrites, therefore the neuronal connectivity map not only depicts the underlying anatomy, but also has important behavioral implications. Different approaches have been utilized to decipher neuronal circuits, including electron microscopy (EM) and light microscopy (LM). However, these approaches typically demand extensive sectioning and reconstruction for a brain sample. Recently, tissue clearing methods have enabled the investigation of a fully assembled biological system with greatly improved light penetration. Yet, most of these implementations, still require either genetic or exogenous contrast labeling for light microscopy. Here we demonstrate a high-speed approach, termed as Clearing Assisted Scattering Tomography (CAST), where intact brains can be imaged at optical resolution without labeling by leveraging tissue clearing and the scattering contrast of optical frequency domain imaging (OFDI).

Optical scatter imaging of cellular and mitochondrial swelling in brain tissue models of stroke

NASA Astrophysics Data System (ADS)

Johnson, Lee James

2001-08-01

The severity of brain edema resulting from a stroke can determine a patient's survival and the extent of their recovery. Cellular swelling is the microscopic source of a significant part of brain edema. Mitochondrial swelling also appears to be a determining event in the death or survival of the cells that are injured during a stroke. Therapies for reducing brain edema are not effective in many cases and current treatments of stroke do not address mitochondrial swelling at all. This dissertation is motivated by the lack of a complete understanding of cellular swelling resulting from stroke and the lack of a good method to begin to study mitochondrial swelling resulting from stroke in living brain tissue. In this dissertation, a novel method of detecting mitochondrial and cellular swelling in living hippocampal slices is developed and validated. The system is used to obtain spatial and temporal information about cellular and mitochondrial swelling resulting from various models of stroke. The effect of changes in water content on light scatter and absorption are examined in two models of brain edema. The results of this study demonstrate that optical techniques can be used to detect changes in water content. Mie scatter theory, the theoretical basis of the dual- angle scatter ratio imaging system, is presented. Computer simulations based on Mie scatter theory are used to determine the optimal angles for imaging. A detailed account of the early systems is presented to explain the motivations for the system design, especially polarization, wavelength and light path. Mitochondrial sized latex particles are used to determine the system response to changes in scattering particle size and concentration. The dual-angle scatter ratio imaging system is used to distinguish between osmotic and excitotoxic models of stroke injury. Such distinction cannot be achieved using the current techniques to study cellular swelling in hippocampal slices. The change in the scatter ratio is then shown to correlate to mitochondrial swelling, as observed with electron microscopy. The system is finally used to study mitochondrial and cellular swelling. Evidence of the susceptibility of certain hippocampal regions, CA1 and the dentate gyrus, to exhibit mitochondrial swelling as the result of oxygen and glucose deprivation is presented. In addition, for the first time, the time course of mitochondrial swelling is seen. Finally, experiments with scatter imaging and measurement of nitric oxide with carbon fiber electrodes demonstrate a clear link between nitric oxide and cellular swelling. A potential mechanism of the action of nitric oxide is evaluated. Nitric oxide appears to act to cause cellular swelling without the release of glutamate. The use of targeted nitric oxide inhibitors may be useful for the reduction of edema.

Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

DTIC Science & Technology

2015-12-01

Hounsfield units (HU) of the brain were translated into corresponding optical properties (absorption coefficient, scattering coefficient, and anisotropy...factor) using lookup tables (Fig 2). The lookup tables were prepared from earlier studies which derived the Hounsfield units and optical properties of... Hounsfield Units /HU) are segmented and translated into optical properties of the brain tissue (white/gray matter, CSF, skull bone, etc.). Monte

Few-mode fiber detection for tissue characterization in optical coherence tomography

NASA Astrophysics Data System (ADS)

Eugui, Pablo; Lichtenegger, Antonia; Augustin, Marco; Harper, Danielle J.; Fialová, Stanislava; Wartak, Andreas; Hitzenberger, Christoph K.; Baumann, Bernhard

2017-07-01

A few-mode fiber based detection for OCT systems is presented. The capability of few-mode fibers for delivering light through different fiber paths enables the application of these fibers for angular scattering tissue character- ization. Since the optical path lengths traveled in the fiber change between the fiber modes, the OCT image information will be reconstructed at different depth positions, separating the directly backscattered light from the light scattered at other angles. Using the proposed method, the relation between the angle of reflection from the sample and the respective modal intensity distribution was investigated. The system was demonstrated for imaging ex-vivo brain tissue samples of patients with Alzheimer's disease.

Transmission in near-infrared optical windows for deep brain imaging.

PubMed

Shi, Lingyan; Sordillo, Laura A; Rodríguez-Contreras, Adrián; Alfano, Robert

2016-01-01

Near-infrared (NIR) radiation has been employed using one- and two-photon excitation of fluorescence imaging at wavelengths 650-950 nm (optical window I) for deep brain imaging; however, longer wavelengths in NIR have been overlooked due to a lack of suitable NIR-low band gap semiconductor imaging detectors and/or femtosecond laser sources. This research introduces three new optical windows in NIR and demonstrates their potential for deep brain tissue imaging. The transmittances are measured in rat brain tissue in the second (II, 1,100-1,350 nm), third (III, 1,600-1,870 nm), and fourth (IV, centered at 2,200 nm) NIR optical tissue windows. The relationship between transmission and tissue thickness is measured and compared with the theory. Due to a reduction in scattering and minimal absorption, window III is shown to be the best for deep brain imaging, and windows II and IV show similar but better potential for deep imaging than window I. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Brain Slice Staining and Preparation for Three-Dimensional Super-Resolution Microscopy

PubMed Central

German, Christopher L.; Gudheti, Manasa V.; Fleckenstein, Annette E.; Jorgensen, Erik M.

2018-01-01

Localization microscopy techniques – such as photoactivation localization microscopy (PALM), fluorescent PALM (FPALM), ground state depletion (GSD), and stochastic optical reconstruction microscopy (STORM) – provide the highest precision for single molecule localization currently available. However, localization microscopy has been largely limited to cell cultures due to the difficulties that arise in imaging thicker tissue sections. Sample fixation and antibody staining, background fluorescence, fluorophore photoinstability, light scattering in thick sections, and sample movement create significant challenges for imaging intact tissue. We have developed a sample preparation and image acquisition protocol to address these challenges in rat brain slices. The sample preparation combined multiple fixation steps, saponin permeabilization, and tissue clarification. Together, these preserve intracellular structures, promote antibody penetration, reduce background fluorescence and light scattering, and allow acquisition of images deep in a 30 μm thick slice. Image acquisition challenges were resolved by overlaying samples with a permeable agarose pad and custom-built stainless steel imaging adapter, and sealing the imaging chamber. This approach kept slices flat, immobile, bathed in imaging buffer, and prevented buffer oxidation during imaging. Using this protocol, we consistently obtained single molecule localizations of synaptic vesicle and active zone proteins in three-dimensions within individual synaptic terminals of the striatum in rat brain slices. These techniques may be easily adapted to the preparation and imaging of other tissues, substantially broadening the application of super-resolution imaging. PMID:28924666

Imaging human brain cyto- and myelo-architecture with quantitative OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Boas, David A.; Wang, Hui; Konukoglu, Ender; Fischl, Bruce; Sakadzic, Sava; Magnain, Caroline V.

2017-02-01

No current imaging technology allows us to directly and without significant distortion visualize the microscopic and defining anatomical features of the human brain. Ex vivo histological techniques can yield exquisite planar images, but the cutting, mounting and staining that are required components of this type of imaging induce distortions that are different for each slice, introducing cross-slice differences that prohibit true 3D analysis. We are overcoming this issue by utilizing Optical Coherence Tomography (OCT) with the goal to image whole human brain cytoarchitectural and laminar properties with potentially 3.5 µm resolution in block-face without the need for exogenous staining. From the intrinsic scattering contrast of the brain tissue, OCT gives us images that are comparable to Nissl stains, but without the distortions introduced in standard histology as the OCT images are acquired from the block face prior to slicing and thus without the need for subsequent staining and mounting. We have shown that laminar and cytoarchitectural properties of the brain can be characterized with OCT just as well as with Nissl staining. We will present our recent advances to improve the axial resolution while maintaining contrast; improvements afforded by speckle reduction procedures; and efforts to obtain quantitative maps of the optical scattering coefficient, an intrinsic property of the tissue.

Dynamic full field OCT: metabolic contrast at subcellular level (Conference Presentation)

NASA Astrophysics Data System (ADS)

Apelian, Clement; Harms, Fabrice; Thouvenin, Olivier; Boccara, Claude A.

2016-03-01

Cells shape or density is an important marker of tissues pathology. However, individual cells are difficult to observe in thick tissues frequently presenting highly scattering structures such as collagen fibers. Endogenous techniques struggle to image cells in these conditions. Moreover, exogenous contrast agents like dyes, fluorophores or nanoparticles cannot always be used, especially if non-invasive imaging is required. Scatterers motion happening down to the millisecond scale, much faster than the still and highly scattering structures (global motion of the tissue), allowed us to develop a new approach based on the time dependence of the FF-OCT signals. This method reveals hidden cells after a spatiotemporal analysis based on singular value decomposition and wavelet analysis concepts. It does also give us access to local dynamics of imaged scatterers. This dynamic information is linked with the local metabolic activity that drives these scatterers. Our technique can explore subcellular scales with micrometric resolution and dynamics ranging from the millisecond to seconds. By this mean we studied a wide range of tissues, animal and human in both normal and pathological conditions (cancer, ischemia, osmotic shock…) in different organs such as liver, kidney, and brain among others. Different cells, undetectable with FF-OCT, were identified (erythrocytes, hepatocytes…). Different scatterers clusters express different characteristic times and thus can be related to different mechanisms that we identify with metabolic functions. We are confident that the D-FFOCT, by accessing to a new spatiotemporal metabolic contrast, will be a leading technique on tissue imaging and for better medical diagnosis.

Subcellular metabolic contrast in living tissue using dynamic full field OCT (D-FFOCT) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Apelian, Clement; Harms, Fabrice; Thouvenin, Olivier; Boccara, Claude A.

2016-03-01

Cells shape or density is an important marker of tissues pathology. However, individual cells are difficult to observe in thick tissues frequently presenting highly scattering structures such as collagen fibers. Endogenous techniques struggle to image cells in these conditions. Moreover, exogenous contrast agents like dyes, fluorophores or nanoparticles cannot always be used, especially if non-invasive imaging is required. Scatterers motion happening down to the millisecond scale, much faster than the fix and highly scattering structures (global motion of the tissue), allowed us to develop a new approach based on the time dependence of the FF-OCT signals. This method reveals hidden cells after a spatiotemporal analysis based on singular value decomposition and wavelet analysis concepts. It does also give us access to local dynamics of imaged scatterers. This dynamic information is linked with the local metabolic activity that drives these scatterers. Our technique can explore subcellular scales with micrometric resolution and dynamics ranging from the millisecond to seconds. By this mean we studied a wide range of tissues, animal and human in both normal and pathological conditions (cancer, ischemia, osmotic shock…) in different organs such as liver, kidney, and brain among others. Different cells, undetectable with FF-OCT, were identified (erythrocytes, hepatocytes…). Different scatterer clusters express different characteristic times and thus can be related to different mechanisms that we identify with metabolic functions. We are confident that the D-FFOCT, by accessing to a new spatiotemporal metabolic contrast, will be a leading technique on tissue imaging and could lead to better medical diagnosis.

Laser-Neuron Interaction with Femtosecond Beat-Modulated 800-1200 nm Photon Beams, as the Treatment of Brain Cancer Tissue. Laser Neurophysics

NASA Astrophysics Data System (ADS)

Stefan, V. Alexander

2011-03-01

I propose a novel mechanism for the brain cancer tissue treatment: nonlinear interaction of ultrashort pulses of beat-photon, (ω1 -- ω2) , or double-photon, (ω1 +ω2) , beams with the cancer tissue. The multiphoton scattering is described via photon diffusion equation. The open-scull cerebral tissue can be irradiated with the beat-modulated photon pulses with the laser irradiances in the range of a few mW/cm2 , and repetition rate of a few 100s Hz generated in the beat-wave driven free electron laser. V. Stefan, B. I. Cohen, and C. Joshi, Nonlinear Mixing of Electromagnetic Waves in PlasmasScience 27 January 1989: V. Alexander Stefan, Genomic Medical Physics: A New Physics in the Making, (S-U-Press, 2008).} This highly accurate cancer tissue ablation removal may prove to be an efficient method for the treatment of brain cancer. Work supported in part by Nikola Tesla Laboratories (Stefan University), La Jolla, CA.

Hybrid Monte Carlo-Diffusion Method For Light Propagation in Tissue With a Low-Scattering Region

NASA Astrophysics Data System (ADS)

Hayashi, Toshiyuki; Kashio, Yoshihiko; Okada, Eiji

2003-06-01

The heterogeneity of the tissues in a head, especially the low-scattering cerebrospinal fluid (CSF) layer surrounding the brain has previously been shown to strongly affect light propagation in the brain. The radiosity-diffusion method, in which the light propagation in the CSF layer is assumed to obey the radiosity theory, has been employed to predict the light propagation in head models. Although the CSF layer is assumed to be a nonscattering region in the radiosity-diffusion method, fine arachnoid trabeculae cause faint scattering in the CSF layer in real heads. A novel approach, the hybrid Monte Carlo-diffusion method, is proposed to calculate the head models, including the low-scattering region in which the light propagation does not obey neither the diffusion approximation nor the radiosity theory. The light propagation in the high-scattering region is calculated by means of the diffusion approximation solved by the finite-element method and that in the low-scattering region is predicted by the Monte Carlo method. The intensity and mean time of flight of the detected light for the head model with a low-scattering CSF layer calculated by the hybrid method agreed well with those by the Monte Carlo method, whereas the results calculated by means of the diffusion approximation included considerable error caused by the effect of the CSF layer. In the hybrid method, the time-consuming Monte Carlo calculation is employed only for the thin CSF layer, and hence, the computation time of the hybrid method is dramatically shorter than that of the Monte Carlo method.

Hybrid Monte Carlo-diffusion method for light propagation in tissue with a low-scattering region.

PubMed

Hayashi, Toshiyuki; Kashio, Yoshihiko; Okada, Eiji

2003-06-01

The heterogeneity of the tissues in a head, especially the low-scattering cerebrospinal fluid (CSF) layer surrounding the brain has previously been shown to strongly affect light propagation in the brain. The radiosity-diffusion method, in which the light propagation in the CSF layer is assumed to obey the radiosity theory, has been employed to predict the light propagation in head models. Although the CSF layer is assumed to be a nonscattering region in the radiosity-diffusion method, fine arachnoid trabeculae cause faint scattering in the CSF layer in real heads. A novel approach, the hybrid Monte Carlo-diffusion method, is proposed to calculate the head models, including the low-scattering region in which the light propagation does not obey neither the diffusion approximation nor the radiosity theory. The light propagation in the high-scattering region is calculated by means of the diffusion approximation solved by the finite-element method and that in the low-scattering region is predicted by the Monte Carlo method. The intensity and mean time of flight of the detected light for the head model with a low-scattering CSF layer calculated by the hybrid method agreed well with those by the Monte Carlo method, whereas the results calculated by means of the diffusion approximation included considerable error caused by the effect of the CSF layer. In the hybrid method, the time-consuming Monte Carlo calculation is employed only for the thin CSF layer, and hence, the computation time of the hybrid method is dramatically shorter than that of the Monte Carlo method.

Fréchet derivative with respect to the shape of a strongly convex nonscattering region in optical tomography

NASA Astrophysics Data System (ADS)

Hyvönen, Nuutti

2007-10-01

The aim of optical tomography is to reconstruct the optical properties inside a physical body, e.g. a neonatal head, by illuminating it with near-infrared light and measuring the outward flux of photons on the object boundary. Because a brain consists of strongly scattering tissue with imbedded cavities filled by weakly scattering cerebrospinal fluid, propagation of near-infrared photons in the human head can be treated by combining the diffusion approximation of the radiative transfer equation with geometrical optics to obtain the radiosity-diffusion forward model of optical tomography. At the moment, a disadvantage with the radiosity-diffusion model is that the locations of the transparent cavities must be known in advance in order to be able to reconstruct the physiologically interesting quantities, i.e., the absorption and the scatter in the strongly scattering brain tissue. In this work we show that the boundary measurement map of optical tomography is Fréchet differentiable with respect to the shape of a strongly convex nonscattering region. Using this result, we introduce a numerical algorithm for approximating an unknown nonscattering cavity by a ball if the background diffuse optical properties of the object are known. The functionality of the method is demonstrated through two-dimensional numerical experiments.

Optical Coherence Tomography for Brain Imaging

NASA Astrophysics Data System (ADS)

Liu, Gangjun; Chen, Zhongping

Recently, there has been growing interest in using OCT for brain imaging. A feasibility study of OCT for guiding deep brain probes has found that OCT can differentiate the white matter and gray matter because the white matter tends to have a higher peak reflectivity and steeper attenuation rate compared to gray matter. In vivo 3D visualization of the layered organization of a rat olfactory bulb with OCT has been demonstrated. OCT has been used for single myelin fiber imaging in living rodents without labeling. The refractive index in the rat somatosensory cortex has also been measured with OCT. In addition, functional extension of OCT, such as Doppler-OCT (D-OCT), polarization sensitive-OCT (PS-OCT), and phase-resolved-OCT (PR-OCT), can image and quantify physiological parameters in addition to the morphological structure image. Based on the scattering changes during neural activity, OCT has been used to measure the functional activation in neuronal tissues. PS-OCT, which combines polarization sensitive detection with OCT to determine tissue birefringence, has been used for the localization of nerve fiber bundles and the mapping of micrometer-scale fiber pathways in the brain. D-OCT, also named optical Doppler tomography (ODT), combines the Doppler principle with OCT to obtain high resolution tomographic images of moving constituents in highly scattering biological tissues. D-OCT has been successfully used to image cortical blood flow and map the blood vessel network for brain research. In this chapter, the principle and technology of OCT and D-OCT are reviewed and examples of potential applications are described.

Imaging cortical absorption, scattering, and hemodynamic response during ischemic stroke using spatially modulated near-infrared illumination

NASA Astrophysics Data System (ADS)

Abookasis, David; Lay, Christopher C.; Mathews, Marlon S.; Linskey, Mark E.; Frostig, Ron D.; Tromberg, Bruce J.

2009-03-01

We describe a technique that uses spatially modulated near-infrared (NIR) illumination to detect and map changes in both optical properties (absorption and reduced scattering parameters) and tissue composition (oxy- and deoxyhemoglobin, total hemoglobin, and oxygen saturation) during acute ischemic injury in the rat barrel cortex. Cerebral ischemia is induced using an open vascular occlusion technique of the middle cerebral artery (MCA). Diffuse reflected NIR light (680 to 980 nm) from the left parietal somatosensory cortex is detected by a CCD camera before and after MCA occlusion. Monte Carlo simulations are used to analyze the spatial frequency dependence of the reflected light to predict spatiotemporal changes in the distribution of tissue absorption and scattering properties in the brain. Experimental results from seven rats show a 17+/-4.7% increase in tissue concentration of deoxyhemoglobin and a 45+/-3.1, 23+/-5.4, and 21+/-2.2% decrease in oxyhemoglobin, total hemoglobin concentration and cerebral tissue oxygen saturation levels, respectively, 45 min following induction of cerebral ischemia. An ischemic index (Iisch=ctHHb/ctO2Hb) reveals an average of more then twofold contrast after MCAo. The wavelength-dependence of the reduced scattering (i.e., scatter power) decreased by 35+/-10.3% after MCA occlusion. Compared to conventional CCD-based intrinsic signal optical imaging (ISOI), the use of structured illumination and model-based analysis allows for generation of separate maps of light absorption and scattering properties as well as tissue hemoglobin concentration. This potentially provides a powerful approach for quantitative monitoring and imaging of neurophysiology and metabolism with high spatiotemporal resolution.

Lithium Visibility in Rat Brain and Muscle in Vivoby 7Li NMR Imaging

NASA Astrophysics Data System (ADS)

Komoroski, Richard A.; Pearce, John M.; Newton, Joseph E. O.

1998-07-01

The apparent concentration of lithium (Li)in vivowas determined for several regions in the brain and muscle of rats by7Li NMR imaging at 4.7 T with inclusion of an external standard of known concentration and visibility. The average apparent concentrations were 10.1 mM for muscle, and 4.2-5.3 mM for various brain regions under the dosing conditions used. The results were compared to concentrations determinedin vitroby high-resolution7Li NMR spectroscopy of extracts of brain and muscle tissue from the same rats. The comparison provided estimates of the7Li NMR visibility of the Li cation in each tissue region. Although there was considerable scatter of the calculated visibilities among the five rats studied, the results suggested essentially full visibility (96%) for Li in muscle, and somewhat reduced visibility (74-93%) in the various brain regions.

Miniature standoff Raman probe for neurosurgical applications

NASA Astrophysics Data System (ADS)

Stevens, Oliver A. C.; Hutchings, Joanne; Gray, William; Vincent, Rosa Louise; Day, John C.

2016-08-01

Removal of intrinsic brain tumors is a delicate process, where a high degree of specificity is required to remove all of the tumor tissue without damaging healthy brain. The accuracy of this process can be greatly enhanced by intraoperative guidance. Optical biopsies using Raman spectroscopy are a minimally invasive and lower-cost alternative to current guidance methods. A miniature Raman probe for performing optical biopsies of human brain tissue is presented. The probe allows sampling inside a conventional stereotactic brain biopsy system: a needle of length 200 mm and inner diameter of 1.8 mm. By employing a miniature stand-off Raman design, the probe removes the need for any additional components to be inserted into the brain. Additionally, the probe achieves a very low internal silica background while maintaining good collection of Raman signal. To illustrate this, the probe is compared with a Raman probe that uses a pair of optical fibers for collection. The miniature stand-off Raman probe is shown to collect a comparable number of Raman scattered photons, but the Raman signal to background ratio is improved by a factor of five at Raman shifts below ˜500 cm-1. The probe's suitability for use on tissue is demonstrated by discriminating between different types of healthy porcine brain tissue.

Super Resolution Imaging of Genetically Labeled Synapses in Drosophila Brain Tissue

PubMed Central

Spühler, Isabelle A.; Conley, Gaurasundar M.; Scheffold, Frank; Sprecher, Simon G.

2016-01-01

Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labeled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation. PMID:27303270

Super Resolution Imaging of Genetically Labeled Synapses in Drosophila Brain Tissue.

PubMed

Spühler, Isabelle A; Conley, Gaurasundar M; Scheffold, Frank; Sprecher, Simon G

2016-01-01

Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labeled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation.

Deep-tissue two-photon imaging in brain and peripheral nerve with a compact high-pulse energy ytterbium fiber laser

NASA Astrophysics Data System (ADS)

Fontaine, Arjun K.; Kirchner, Matthew S.; Caldwell, John H.; Weir, Richard F.; Gibson, Emily A.

2018-02-01

Two-photon microscopy is a powerful tool of current scientific research, allowing optical visualization of structures below the surface of tissues. This is of particular value in neuroscience, where optically accessing regions within the brain is critical for the continued advancement in understanding of neural circuits. However, two-photon imaging at significant depths have typically used Ti:Sapphire based amplifiers that are prohibitively expensive and bulky. In this study, we demonstrate deep tissue two-photon imaging using a compact, inexpensive, turnkey operated Ytterbium fiber laser (Y-Fi, KM Labs). The laser is based on all-normal dispersion (ANDi) that provides short pulse durations and high pulse energies. Depth measurements obtained in ex vivo mouse cortex exceed those obtainable with standard two-photon microscopes using Ti:Sapphire lasers. In addition to demonstrating the capability of deep-tissue imaging in the brain, we investigated imaging depth in highly-scattering white matter with measurements in sciatic nerve showing limited optical penetration of heavily myelinated nerve tissue relative to grey matter.

A fast atlas-guided high density diffuse optical tomography system for brain imaging

NASA Astrophysics Data System (ADS)

Dai, Xianjin; Zhang, Tao; Yang, Hao; Jiang, Huabei

2017-02-01

Near infrared spectroscopy (NIRS) is an emerging functional brain imaging tool capable of assessing cerebral concentrations of oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) during brain activation noninvasively. As an extension of NIRS, diffuse optical tomography (DOT) not only shares the merits of providing continuous readings of cerebral oxygenation, but also has the ability to provide spatial resolution in the millimeter scale. Based on the scattering and absorption properties of nonionizing near-infrared light in biological tissue, DOT has been successfully applied in the imaging of breast tumors, osteoarthritis and cortex activations. Here, we present a state-of-art fast high density DOT system suitable for brain imaging. It can achieve up to a 21 Hz sampling rate for a full set of two-wavelength data for 3-D DOT brain image reconstruction. The system was validated using tissue-mimicking brain-model phantom. Then, experiments on healthy subjects were conducted to demonstrate the capability of the system.

TOPICAL REVIEW: Human soft tissue analysis using x-ray or gamma-ray techniques

NASA Astrophysics Data System (ADS)

Theodorakou, C.; Farquharson, M. J.

2008-06-01

This topical review is intended to describe the x-ray techniques used for human soft tissue analysis. X-ray techniques have been applied to human soft tissue characterization and interesting results have been presented over the last few decades. The motivation behind such studies is to provide improved patient outcome by using the data obtained to better understand a disease process and improve diagnosis. An overview of theoretical background as well as a complete set of references is presented. For each study, a brief summary of the methodology and results is given. The x-ray techniques include x-ray diffraction, x-ray fluorescence, Compton scattering, Compton to coherent scattering ratio and attenuation measurements. The soft tissues that have been classified using x-rays or gamma rays include brain, breast, colon, fat, kidney, liver, lung, muscle, prostate, skin, thyroid and uterus.

Diffuse optical tomography and spectroscopy of breast cancer and fetal brain

NASA Astrophysics Data System (ADS)

Choe, Regine

Diffuse optical techniques utilize light in the near infrared spectral range to measure tissue physiology non-invasively. Based on these measurements, either on average or a three-dimensional spatial map of tissue properties such as total hemoglobin concentration, blood oxygen saturation and scattering can be obtained using model-based reconstruction algorithms. In this thesis, diffuse optical techniques were applied for in vivo breast cancer imaging and trans-abdominal fetal brain oxygenation monitoring. For in vivo breast cancer imaging, clinical diffuse optical tomography and related instrumentation was developed and used in several contexts. Bulk physiological properties were quantified for fifty-two healthy subjects in the parallel-plate transmission geometry. Three-dimensional images of breast were reconstructed for subjects with breast tumors and, tumor contrast with respect to normal tissue was found in total hemoglobin concentration and scattering and was quantified for twenty-two breast carcinomas. Tumor contrast and tumor volume changes during neoadjuvant chemotherapy were tracked for one subject and compared to the dynamic contrast-enhanced MRI. Finally, the feasibility for measuring blood flow of breast tumors using optical methods was demonstrated for seven subjects. In a qualitatively different set of experiments, the feasibility for trans-abdominal fetal brain oxygenation monitoring was demonstrated on pregnant ewes with induced fetal hypoxia. Preliminary clinical experiences were discussed to identify future directions. In total, this research has translated diffuse optical tomography techniques into clinical research environment.

Fast wavefront optimization for focusing through biological tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Blochet, Baptiste; Bourdieu, Laurent; Gigan, Sylvain

2017-02-01

The propagation of light in biological tissues is rapidly dominated by multiple scattering: ballistic light is exponentially attenuated, which limits the penetration depth of conventional microscopy techniques. For coherent light, the recombination of the different scattered paths creates a complex interference: speckle. Recently, different wavefront shaping techniques have been developed to coherently manipulate the speckle. It opens the possibility to focus light through complex media and ultimately to image in them, provided however that the medium can be considered as stationary. We have studied the possibility to focus in and through time-varying biological tissues. Their intrinsic temporal dynamics creates a fast decorrelation of the speckle pattern. Therefore, focusing through biological tissues requires fast wavefront shaping devices, sensors and algorithms. We have investigated the use of a MEMS-based spatial light modulator (SLM) and a fast photodetector, combined with FPGA electronics to implement a closed-loop optimization. Our optimization process is just limited by the temporal dynamics of the SLM (200µs) and the computation time (45µs), thus corresponding to a rate of 4 kHz. To our knowledge, it's the fastest closed loop optimization using phase modulators. We have studied the focusing through colloidal solutions of TiO2 particles in glycerol, allowing tunable temporal stability, and scattering properties similar to biological tissues. We have shown that our set-up fulfills the required characteristics (speed, enhancement) to focus through biological tissues. We are currently investigating the focusing through acute rat brain slices and the memory effect in dynamic scattering media.

Modeling bioluminescent photon transport in tissue based on Radiosity-diffusion model

NASA Astrophysics Data System (ADS)

Sun, Li; Wang, Pu; Tian, Jie; Zhang, Bo; Han, Dong; Yang, Xin

2010-03-01

Bioluminescence tomography (BLT) is one of the most important non-invasive optical molecular imaging modalities. The model for the bioluminescent photon propagation plays a significant role in the bioluminescence tomography study. Due to the high computational efficiency, diffusion approximation (DA) is generally applied in the bioluminescence tomography. But the diffusion equation is valid only in highly scattering and weakly absorbing regions and fails in non-scattering or low-scattering tissues, such as a cyst in the breast, the cerebrospinal fluid (CSF) layer of the brain and synovial fluid layer in the joints. A hybrid Radiosity-diffusion model is proposed for dealing with the non-scattering regions within diffusing domains in this paper. This hybrid method incorporates a priori information of the geometry of non-scattering regions, which can be acquired by magnetic resonance imaging (MRI) or x-ray computed tomography (CT). Then the model is implemented using a finite element method (FEM) to ensure the high computational efficiency. Finally, we demonstrate that the method is comparable with Mont Carlo (MC) method which is regarded as a 'gold standard' for photon transportation simulation.

High-speed spatial frequency domain imaging of rat cortex detects dynamic optical and physiological properties following cardiac arrest and resuscitation.

PubMed

Wilson, Robert H; Crouzet, Christian; Torabzadeh, Mohammad; Bazrafkan, Afsheen; Farahabadi, Maryam H; Jamasian, Babak; Donga, Dishant; Alcocer, Juan; Zaher, Shuhab M; Choi, Bernard; Akbari, Yama; Tromberg, Bruce J

2017-10-01

Quantifying rapidly varying perturbations in cerebral tissue absorption and scattering can potentially help to characterize changes in brain function caused by ischemic trauma. We have developed a platform for rapid intrinsic signal brain optical imaging using macroscopically structured light. The device performs fast, multispectral, spatial frequency domain imaging (SFDI), detecting backscattered light from three-phase binary square-wave projected patterns, which have a much higher refresh rate than sinusoidal patterns used in conventional SFDI. Although not as fast as "single-snapshot" spatial frequency methods that do not require three-phase projection, square-wave patterns allow accurate image demodulation in applications such as small animal imaging where the limited field of view does not allow single-phase demodulation. By using 655, 730, and 850 nm light-emitting diodes, two spatial frequencies ([Formula: see text] and [Formula: see text]), three spatial phases (120 deg, 240 deg, and 360 deg), and an overall camera acquisition rate of 167 Hz, we map changes in tissue absorption and reduced scattering parameters ([Formula: see text] and [Formula: see text]) and oxy- and deoxyhemoglobin concentration at [Formula: see text]. We apply this method to a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) to quantify hemodynamics and scattering on temporal scales ([Formula: see text]) ranging from tens of milliseconds to minutes. We observe rapid concurrent spatiotemporal changes in tissue oxygenation and scattering during CA and following CPR, even when the cerebral electrical signal is absent. We conclude that square-wave SFDI provides an effective technical strategy for assessing cortical optical and physiological properties by balancing competing performance demands for fast signal acquisition, small fields of view, and quantitative information content.

High-fidelity artifact correction for cone-beam CT imaging of the brain

NASA Astrophysics Data System (ADS)

Sisniega, A.; Zbijewski, W.; Xu, J.; Dang, H.; Stayman, J. W.; Yorkston, J.; Aygun, N.; Koliatsos, V.; Siewerdsen, J. H.

2015-02-01

CT is the frontline imaging modality for diagnosis of acute traumatic brain injury (TBI), involving the detection of fresh blood in the brain (contrast of 30-50 HU, detail size down to 1 mm) in a non-contrast-enhanced exam. A dedicated point-of-care imaging system based on cone-beam CT (CBCT) could benefit early detection of TBI and improve direction to appropriate therapy. However, flat-panel detector (FPD) CBCT is challenged by artifacts that degrade contrast resolution and limit application in soft-tissue imaging. We present and evaluate a fairly comprehensive framework for artifact correction to enable soft-tissue brain imaging with FPD CBCT. The framework includes a fast Monte Carlo (MC)-based scatter estimation method complemented by corrections for detector lag, veiling glare, and beam hardening. The fast MC scatter estimation combines GPU acceleration, variance reduction, and simulation with a low number of photon histories and reduced number of projection angles (sparse MC) augmented by kernel de-noising to yield a runtime of ~4 min per scan. Scatter correction is combined with two-pass beam hardening correction. Detector lag correction is based on temporal deconvolution of the measured lag response function. The effects of detector veiling glare are reduced by deconvolution of the glare response function representing the long range tails of the detector point-spread function. The performance of the correction framework is quantified in experiments using a realistic head phantom on a testbench for FPD CBCT. Uncorrected reconstructions were non-diagnostic for soft-tissue imaging tasks in the brain. After processing with the artifact correction framework, image uniformity was substantially improved, and artifacts were reduced to a level that enabled visualization of ~3 mm simulated bleeds throughout the brain. Non-uniformity (cupping) was reduced by a factor of 5, and contrast of simulated bleeds was improved from ~7 to 49.7 HU, in good agreement with the nominal blood contrast of 50 HU. Although noise was amplified by the corrections, the contrast-to-noise ratio (CNR) of simulated bleeds was improved by nearly a factor of 3.5 (CNR = 0.54 without corrections and 1.91 after correction). The resulting image quality motivates further development and translation of the FPD-CBCT system for imaging of acute TBI.

Three-dimensional light-tissue interaction models for bioluminescence tomography

NASA Astrophysics Data System (ADS)

Côté, D.; Allard, M.; Henkelman, R. M.; Vitkin, I. A.

2005-09-01

Many diagnostic and therapeutic approaches in medical physics today take advantage of the unique properties of light and its interaction with tissues. Because light scatters in tissue, our ability to develop these techniques depends critically on our knowledge of the distribution of light in tissue. Solutions to the diffusion equation can provide such information, but often lack the flexibility required for more general problems that involve, for instance, inhomogeneous optical properties, light polarization, arbitrary three-dimensional geometries, or arbitrary scattering. Monte Carlo techniques, which statistically sample the light distribution in tissue, offer a better alternative to analytical models. First, we discuss our implementation of a validated three-dimensional polarization-sensitive Monte Carlo algorithm and demonstrate its generality with respect to the geometry and scattering models it can treat. Second, we apply our model to bioluminescence tomography. After appropriate genetic modifications to cell lines, bioluminescence can be used as an indicator of cell activity, and is often used to study tumour growth and treatment in animal models. However, the amount of light escaping the animal is strongly dependent on the position and size of the tumour. Using forward models and structural data from magnetic resonance imaging, we show how the models can help to determine the location and size of tumour made of bioluminescent cancer cells in the brain of a mouse.

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, P; Park, P; Li, H

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated withmore » PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.« less

Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light

PubMed Central

Ruan, Haowen; Brake, Joshua; Robinson, J. Elliott; Liu, Yan; Jang, Mooseok; Xiao, Cheng; Zhou, Chunyi; Gradinaru, Viviana; Yang, Changhuei

2017-01-01

Noninvasive light focusing deep inside living biological tissue has long been a goal in biomedical optics. However, the optical scattering of biological tissue prevents conventional optical systems from tightly focusing visible light beyond several hundred micrometers. The recently developed wavefront shaping technique time-reversed ultrasonically encoded (TRUE) focusing enables noninvasive light delivery to targeted locations beyond the optical diffusion limit. However, until now, TRUE focusing has only been demonstrated inside nonliving tissue samples. We present the first example of TRUE focusing in 2-mm-thick living brain tissue and demonstrate its application for optogenetic modulation of neural activity in 800-μm-thick acute mouse brain slices at a wavelength of 532 nm. We found that TRUE focusing enabled precise control of neuron firing and increased the spatial resolution of neuronal excitation fourfold when compared to conventional lens focusing. This work is an important step in the application of TRUE focusing for practical biomedical uses. PMID:29226248

Geometrically complex 3D-printed phantoms for diffuse optical imaging.

PubMed

Dempsey, Laura A; Persad, Melissa; Powell, Samuel; Chitnis, Danial; Hebden, Jeremy C

2017-03-01

Tissue-equivalent phantoms that mimic the optical properties of human and animal tissues are commonly used in diffuse optical imaging research to characterize instrumentation or evaluate an image reconstruction method. Although many recipes have been produced for generating solid phantoms with specified absorption and transport scattering coefficients at visible and near-infrared wavelengths, the construction methods are generally time-consuming and are unable to create complex geometries. We present a method of generating phantoms using a standard 3D printer. A simple recipe was devised which enables printed phantoms to be produced with precisely known optical properties. To illustrate the capability of the method, we describe the creation of an anatomically accurate, tissue-equivalent premature infant head optical phantom with a hollow brain space based on MRI atlas data. A diffuse optical image of the phantom is acquired when a high contrast target is inserted into the hollow space filled with an aqueous scattering solution.

Geometrically complex 3D-printed phantoms for diffuse optical imaging

PubMed Central

Dempsey, Laura A.; Persad, Melissa; Powell, Samuel; Chitnis, Danial; Hebden, Jeremy C.

2017-01-01

Tissue-equivalent phantoms that mimic the optical properties of human and animal tissues are commonly used in diffuse optical imaging research to characterize instrumentation or evaluate an image reconstruction method. Although many recipes have been produced for generating solid phantoms with specified absorption and transport scattering coefficients at visible and near-infrared wavelengths, the construction methods are generally time-consuming and are unable to create complex geometries. We present a method of generating phantoms using a standard 3D printer. A simple recipe was devised which enables printed phantoms to be produced with precisely known optical properties. To illustrate the capability of the method, we describe the creation of an anatomically accurate, tissue-equivalent premature infant head optical phantom with a hollow brain space based on MRI atlas data. A diffuse optical image of the phantom is acquired when a high contrast target is inserted into the hollow space filled with an aqueous scattering solution. PMID:28663863

White matter segmentation by estimating tissue optical attenuation from volumetric OCT massive histology of whole rodent brains

NASA Astrophysics Data System (ADS)

Lefebvre, Joël.; Castonguay, Alexandre; Lesage, Frédéric

2017-02-01

A whole rodent brain was imaged using an automated massive histology setup and an Optical Coherence Tomography (OCT) microscope. Thousands of OCT volumetric tiles were acquired, each covering a size of about 2.5x2.5x0.8 mm3 with a sampling resolution of 4.9x4.9x6.5 microns. This paper shows the techniques for reconstruction, attenuation compensation and segmentation of the sliced brains. The tile positions within the mosaic were evaluated using a displacement model of the motorized stage and pairwise coregistration. Volume blending was then performed by solving the 3D Laplace equation, and consecutive slices were assembled using the cross-correlation of their 2D image gradient. This reconstruction algorithm resulted in a 3D map of optical reflectivity for the whole brain at micrometric resolution. OCT tissue slices were then used to estimate the local attenuation coefficient based on a single scattering photon model. The attenuation map obtained exhibits a high contrast for all white matter fibres, regardless of their orientation. The tissue optical attenuation from the intrinsic OCT reflectivity contributes to better white matter tissue segmentation. The combined 3D maps of reflectivity and attenuation is a step toward the study of white matter at a microscopic scale for the whole brain in small animals.

Comparison of seven optical clearing methods for mouse brain

NASA Astrophysics Data System (ADS)

Wan, Peng; Zhu, Jingtan; Yu, Tingting; Zhu, Dan

2018-02-01

Recently, a variety of tissue optical clearing techniques have been developed to reduce light scattering for imaging deeper and three-dimensional reconstruction of tissue structures. Combined with optical imaging techniques and diverse labeling methods, these clearing methods have significantly promoted the development of neuroscience. However, most of the protocols were proposed aiming for specific tissue type. Though there are some comparison results, the clearing methods covered are limited and the evaluation indices are lack of uniformity, which made it difficult to select a best-fit protocol for clearing in practical applications. Hence, it is necessary to systematically assess and compare these clearing methods. In this work, we evaluated the performance of seven typical clearing methods, including 3DISCO, uDISCO, SeeDB, ScaleS, ClearT2, CUBIC and PACT, on mouse brain samples. First, we compared the clearing capability on both brain slices and whole-brains by observing brain transparency. Further, we evaluated the fluorescence preservation and the increase of imaging depth. The results showed that 3DISCO, uDISCO and PACT posed excellent clearing capability on mouse brains, ScaleS and SeeDB rendered moderate transparency, while ClearT2 was the worst. Among those methods, ScaleS was the best on fluorescence preservation, and PACT achieved the highest increase of imaging depth. This study is expected to provide important reference for users in choosing most suitable brain optical clearing method.

Listening to light scattering in turbid media: quantitative optical scattering imaging using photoacoustic measurements with one-wavelength illumination

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Li, Xiaoqi; Xi, Lei

2014-06-01

Biomedical photoacoustic tomography (PAT), as a potential imaging modality, can visualize tissue structure and function with high spatial resolution and excellent optical contrast. It is widely recognized that the ability of quantitatively imaging optical absorption and scattering coefficients from photoacoustic measurements is essential before PAT can become a powerful imaging modality. Existing quantitative PAT (qPAT), while successful, has been focused on recovering absorption coefficient only by assuming scattering coefficient a constant. An effective method for photoacoustically recovering optical scattering coefficient is presently not available. Here we propose and experimentally validate such a method for quantitative scattering coefficient imaging using photoacoustic data from one-wavelength illumination. The reconstruction method developed combines conventional PAT with the photon diffusion equation in a novel way to realize the recovery of scattering coefficient. We demonstrate the method using various objects having scattering contrast only or both absorption and scattering contrasts embedded in turbid media. The listening-to-light-scattering method described will be able to provide high resolution scattering imaging for various biomedical applications ranging from breast to brain imaging.

Physical principles for scalable neural recording

PubMed Central

Zamft, Bradley M.; Maguire, Yael G.; Shapiro, Mikhail G.; Cybulski, Thaddeus R.; Glaser, Joshua I.; Amodei, Dario; Stranges, P. Benjamin; Kalhor, Reza; Dalrymple, David A.; Seo, Dongjin; Alon, Elad; Maharbiz, Michel M.; Carmena, Jose M.; Rabaey, Jan M.; Boyden, Edward S.; Church, George M.; Kording, Konrad P.

2013-01-01

Simultaneously measuring the activities of all neurons in a mammalian brain at millisecond resolution is a challenge beyond the limits of existing techniques in neuroscience. Entirely new approaches may be required, motivating an analysis of the fundamental physical constraints on the problem. We outline the physical principles governing brain activity mapping using optical, electrical, magnetic resonance, and molecular modalities of neural recording. Focusing on the mouse brain, we analyze the scalability of each method, concentrating on the limitations imposed by spatiotemporal resolution, energy dissipation, and volume displacement. Based on this analysis, all existing approaches require orders of magnitude improvement in key parameters. Electrical recording is limited by the low multiplexing capacity of electrodes and their lack of intrinsic spatial resolution, optical methods are constrained by the scattering of visible light in brain tissue, magnetic resonance is hindered by the diffusion and relaxation timescales of water protons, and the implementation of molecular recording is complicated by the stochastic kinetics of enzymes. Understanding the physical limits of brain activity mapping may provide insight into opportunities for novel solutions. For example, unconventional methods for delivering electrodes may enable unprecedented numbers of recording sites, embedded optical devices could allow optical detectors to be placed within a few scattering lengths of the measured neurons, and new classes of molecularly engineered sensors might obviate cumbersome hardware architectures. We also study the physics of powering and communicating with microscale devices embedded in brain tissue and find that, while radio-frequency electromagnetic data transmission suffers from a severe power–bandwidth tradeoff, communication via infrared light or ultrasound may allow high data rates due to the possibility of spatial multiplexing. The use of embedded local recording and wireless data transmission would only be viable, however, given major improvements to the power efficiency of microelectronic devices. PMID:24187539

Amyloid structure exhibits polymorphism on multiple length scales in human brain tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Jiliang; Costantino, Isabel; Venugopalan, Nagarajan

Although aggregation of Aβ amyloid fibrils into plaques in the brain is a hallmark of Alzheimer's Disease (AD), the correlation between amyloid burden and severity of symptoms is weak. One possible reason is that amyloid fibrils are structurally polymorphic and different polymorphs may contribute differentially to disease. However, the occurrence and distribution of amyloid polymorphisms in human brain is poorly documented. Here we seek to fill this knowledge gap by using X-ray microdiffraction of histological sections of human tissue to map the abundance, orientation and structural heterogeneities of amyloid within individual plaques; among proximal plaques and in subjects with distinctmore » clinical histories. A 5 µ x-ray beam was used to generate diffraction data with each pattern arising from a scattering volume of only ~ 450 µ3 , making possible collection of dozens to hundreds of diffraction patterns from a single amyloid plaque. X-ray scattering from these samples exhibited all the properties expected for scattering from amyloid. Amyloid distribution was mapped using the intensity of its signature 4.7 Å reflection which also provided information on the orientation of amyloid fibrils across plaques. Margins of plaques exhibited a greater degree of orientation than cores and orientation around blood vessels frequently appeared tangential. Variation in the structure of Aβ fibrils is reflected in the shape of the 4.7 Å peak which usually appears as a doublet. Variations in this peak correspond to differences between the structure of amyloid within cores of plaques and at their periphery. Examination of tissue from a mismatch case - an individual with high plaque burden but no overt signs of dementia at time of death - revealed a diversity of structure and spatial distribution of amyloid that is distinct from typical AD cases. We demonstrate the existence of structural polymorphisms among amyloid within and among plaques of a single individual and suggest the existence of distinct differences in the organization of amyloid in subjects with different clinical presentations.« less

Amyloid structure exhibits polymorphism on multiple length scales in human brain tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Jiliang; Costantino, Isabel; Venugopalan, Nagarajan

Although aggregation of Aβ amyloid fibrils into plaques in the brain is a hallmark of Alzheimer's Disease (AD), the correlation between amyloid burden and severity of symptoms is weak. One possible reason is that amyloid fibrils are structurally polymorphic and different polymorphs may contribute differentially to disease. However, the occurrence and distribution of amyloid polymorphisms in human brain is poorly documented. Here we seek to fill this knowledge gap by using X-ray microdiffraction of histological sections of human tissue to map the abundance, orientation and structural heterogeneities of amyloid within individual plaques; among proximal plaques and in subjects with distinctmore » clinical histories. A 5 µ x-ray beam was used to generate diffraction data with each pattern arising from a scattering volume of only ~ 450 µ3 , making possible collection of dozens to hundreds of diffraction patterns from a single amyloid plaque. X-ray scattering from these samples exhibited all the properties expected for scattering from amyloid. Amyloid distribution was mapped using the intensity of its signature 4.7 Å reflection which also provided information on the orientation of amyloid fibrils across plaques. Margins of plaques exhibited a greater degree of orientation than cores and orientation around blood vessels frequently appeared tangential. Variation in the structure of Aβ fibrils is reflected in the shape of the 4.7 Å peak which usually appears as a doublet. Variations in this peak correspond to differences between the structure of amyloid within cores of plaques and at their periphery. Examination of tissue from a mismatch case - an individual with high plaque burden but no overt signs of dementia at time of death - revealed a diversity of structure and spatial distribution of amyloid that is distinct from typical AD cases. As a result, we demonstrate the existence of structural polymorphisms among amyloid within and among plaques of a single individual and suggest the existence of distinct differences in the organization of amyloid in subjects with different clinical presentations.« less

Amyloid structure exhibits polymorphism on multiple length scales in human brain tissue

DOE PAGES

Liu, Jiliang; Costantino, Isabel; Venugopalan, Nagarajan; ...

2016-09-15

Although aggregation of Aβ amyloid fibrils into plaques in the brain is a hallmark of Alzheimer's Disease (AD), the correlation between amyloid burden and severity of symptoms is weak. One possible reason is that amyloid fibrils are structurally polymorphic and different polymorphs may contribute differentially to disease. However, the occurrence and distribution of amyloid polymorphisms in human brain is poorly documented. Here we seek to fill this knowledge gap by using X-ray microdiffraction of histological sections of human tissue to map the abundance, orientation and structural heterogeneities of amyloid within individual plaques; among proximal plaques and in subjects with distinctmore » clinical histories. A 5 µ x-ray beam was used to generate diffraction data with each pattern arising from a scattering volume of only ~ 450 µ3 , making possible collection of dozens to hundreds of diffraction patterns from a single amyloid plaque. X-ray scattering from these samples exhibited all the properties expected for scattering from amyloid. Amyloid distribution was mapped using the intensity of its signature 4.7 Å reflection which also provided information on the orientation of amyloid fibrils across plaques. Margins of plaques exhibited a greater degree of orientation than cores and orientation around blood vessels frequently appeared tangential. Variation in the structure of Aβ fibrils is reflected in the shape of the 4.7 Å peak which usually appears as a doublet. Variations in this peak correspond to differences between the structure of amyloid within cores of plaques and at their periphery. Examination of tissue from a mismatch case - an individual with high plaque burden but no overt signs of dementia at time of death - revealed a diversity of structure and spatial distribution of amyloid that is distinct from typical AD cases. As a result, we demonstrate the existence of structural polymorphisms among amyloid within and among plaques of a single individual and suggest the existence of distinct differences in the organization of amyloid in subjects with different clinical presentations.« less

A versatile clearing agent for multi-modal brain imaging

PubMed Central

Costantini, Irene; Ghobril, Jean-Pierre; Di Giovanna, Antonino Paolo; Mascaro, Anna Letizia Allegra; Silvestri, Ludovico; Müllenbroich, Marie Caroline; Onofri, Leonardo; Conti, Valerio; Vanzi, Francesco; Sacconi, Leonardo; Guerrini, Renzo; Markram, Henry; Iannello, Giulio; Pavone, Francesco Saverio

2015-01-01

Extensive mapping of neuronal connections in the central nervous system requires high-throughput µm-scale imaging of large volumes. In recent years, different approaches have been developed to overcome the limitations due to tissue light scattering. These methods are generally developed to improve the performance of a specific imaging modality, thus limiting comprehensive neuroanatomical exploration by multi-modal optical techniques. Here, we introduce a versatile brain clearing agent (2,2′-thiodiethanol; TDE) suitable for various applications and imaging techniques. TDE is cost-efficient, water-soluble and low-viscous and, more importantly, it preserves fluorescence, is compatible with immunostaining and does not cause deformations at sub-cellular level. We demonstrate the effectiveness of this method in different applications: in fixed samples by imaging a whole mouse hippocampus with serial two-photon tomography; in combination with CLARITY by reconstructing an entire mouse brain with light sheet microscopy and in translational research by imaging immunostained human dysplastic brain tissue. PMID:25950610

TH-A-18C-09: Ultra-Fast Monte Carlo Simulation for Cone Beam CT Imaging of Brain Trauma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sisniega, A; Zbijewski, W; Stayman, J

Purpose: Application of cone-beam CT (CBCT) to low-contrast soft tissue imaging, such as in detection of traumatic brain injury, is challenged by high levels of scatter. A fast, accurate scatter correction method based on Monte Carlo (MC) estimation is developed for application in high-quality CBCT imaging of acute brain injury. Methods: The correction involves MC scatter estimation executed on an NVIDIA GTX 780 GPU (MC-GPU), with baseline simulation speed of ~1e7 photons/sec. MC-GPU is accelerated by a novel, GPU-optimized implementation of variance reduction (VR) techniques (forced detection and photon splitting). The number of simulated tracks and projections is reduced formore » additional speed-up. Residual noise is removed and the missing scatter projections are estimated via kernel smoothing (KS) in projection plane and across gantry angles. The method is assessed using CBCT images of a head phantom presenting a realistic simulation of fresh intracranial hemorrhage (100 kVp, 180 mAs, 720 projections, source-detector distance 700 mm, source-axis distance 480 mm). Results: For a fixed run-time of ~1 sec/projection, GPU-optimized VR reduces the noise in MC-GPU scatter estimates by a factor of 4. For scatter correction, MC-GPU with VR is executed with 4-fold angular downsampling and 1e5 photons/projection, yielding 3.5 minute run-time per scan, and de-noised with optimized KS. Corrected CBCT images demonstrate uniformity improvement of 18 HU and contrast improvement of 26 HU compared to no correction, and a 52% increase in contrast-tonoise ratio in simulated hemorrhage compared to “oracle” constant fraction correction. Conclusion: Acceleration of MC-GPU achieved through GPU-optimized variance reduction and kernel smoothing yields an efficient (<5 min/scan) and accurate scatter correction that does not rely on additional hardware or simplifying assumptions about the scatter distribution. The method is undergoing implementation in a novel CBCT dedicated to brain trauma imaging at the point of care in sports and military applications. Research grant from Carestream Health. JY is an employee of Carestream Health.« less

Measurement of light transmission and fluence rate in mouse brain in vivo(Conference Presentation)

NASA Astrophysics Data System (ADS)

Macklin, John J.; Graves, Austin R.; Stujenske, Joseph M.; Hantman, Adam W.; Bittner, Katie C.

2017-02-01

Optogenetic experiments require light delivery, typically using fiber optics, to light-gated ion channels genetically targeted to specific brain regions. Understanding where light is—and isn't—in an illuminated brain can be a confounding factor in designing experiments and interpreting results. While the transmission of light, i.e. survival of forward-directed and forward-scattered light, has been extensively measured in vitro, light scattering can be significantly different in vivo due to blood flow and other factors. To measure irradiance in vivo, we constructed a pipette photodetector tipped with fluorescent quantum dots that function as a light transducer. The quantum dot fluorescence is collected by a waveguide and sent to a fiber-coupled spectrometer. The device has a small photo-responsive area ( 10 um x 15 um), enabling collection of micron-resolution irradiance profiles, and can be calibrated to determine irradiance with detection limits of 0.001 mW/mm2. The photodetector has the footprint of a micro-injection pipette, so can be inserted into almost any brain region with minimal invasiveness. With this detector, we determined transverse and axial irradiance profiles in mice across multiple brain regions at 5 source wavelengths spanning the visible spectrum. This profile data is compared to in vitro measurements obtained on tissue slices, and provides a means to derive scattering coefficients for specific brain regions in vivo. The detector is straightforward to fabricate and calibrate, is stable in air storage > 9 months, and can be easily installed in an electrophysiology setup, thereby enabling direct measurement of light spread under conditions used in optogenetics experiments.

Shack-Hartmann wavefront-sensor-based adaptive optics system for multiphoton microscopy

PubMed Central

Cha, Jae Won; Ballesta, Jerome; So, Peter T.C.

2010-01-01

The imaging depth of two-photon excitation fluorescence microscopy is partly limited by the inhomogeneity of the refractive index in biological specimens. This inhomogeneity results in a distortion of the wavefront of the excitation light. This wavefront distortion results in image resolution degradation and lower signal level. Using an adaptive optics system consisting of a Shack-Hartmann wavefront sensor and a deformable mirror, wavefront distortion can be measured and corrected. With adaptive optics compensation, we demonstrate that the resolution and signal level can be better preserved at greater imaging depth in a variety of ex-vivo tissue specimens including mouse tongue muscle, heart muscle, and brain. However, for these highly scattering tissues, we find signal degradation due to scattering to be a more dominant factor than aberration. PMID:20799824

Shack-Hartmann wavefront-sensor-based adaptive optics system for multiphoton microscopy.

PubMed

Cha, Jae Won; Ballesta, Jerome; So, Peter T C

2010-01-01

The imaging depth of two-photon excitation fluorescence microscopy is partly limited by the inhomogeneity of the refractive index in biological specimens. This inhomogeneity results in a distortion of the wavefront of the excitation light. This wavefront distortion results in image resolution degradation and lower signal level. Using an adaptive optics system consisting of a Shack-Hartmann wavefront sensor and a deformable mirror, wavefront distortion can be measured and corrected. With adaptive optics compensation, we demonstrate that the resolution and signal level can be better preserved at greater imaging depth in a variety of ex-vivo tissue specimens including mouse tongue muscle, heart muscle, and brain. However, for these highly scattering tissues, we find signal degradation due to scattering to be a more dominant factor than aberration.

High-refractive index of acrylate embedding resin clarifies mouse brain tissue

NASA Astrophysics Data System (ADS)

Zhou, Hongfu; Xiong, Yumiao; Wang, Yu; Wang, Xiaojun; Li, Pei; Gang, Yadong; Liu, Xiuli; Zeng, Shaoqun

2017-11-01

Biological tissue transparency combined with light-sheet fluorescence microscopy is a useful method for studying the neural structure of biological tissues. The development of light-sheet fluorescence microscopy also promotes progress in biological tissue clearing methods. The current clarifying methods mostly use liquid reagent to denature protein or remove lipids first, to eliminate or reduce the scattering index or refractive index of the biological tissue. However, denaturing protein and removing lipids require complex procedures or an extended time period. Therefore, here we have developed acrylate resin with a high refractive index, which causes clearing of biological tissue directly after polymerization. This method can improve endogenous fluorescence retention by adjusting the pH value of the resin monomer.

Whole-head functional brain imaging of neonates at cot-side using time-resolved diffuse optical tomography

NASA Astrophysics Data System (ADS)

Dempsey, Laura A.; Cooper, Robert J.; Powell, Samuel; Edwards, Andrea; Lee, Chuen-Wai; Brigadoi, Sabrina; Everdell, Nick; Arridge, Simon; Gibson, Adam P.; Austin, Topun; Hebden, Jeremy C.

2015-07-01

We present a method for acquiring whole-head images of changes in blood volume and oxygenation from the infant brain at cot-side using time-resolved diffuse optical tomography (TR-DOT). At UCL, we have built a portable TR-DOT device, known as MONSTIR II, which is capable of obtaining a whole-head (1024 channels) image sequence in 75 seconds. Datatypes extracted from the temporal point spread functions acquired by the system allow us to determine changes in absorption and reduced scattering coefficients within the interrogated tissue. This information can then be used to define clinically relevant measures, such as oxygen saturation, as well as to reconstruct images of relative changes in tissue chromophore concentration, notably those of oxy- and deoxyhaemoglobin. Additionally, the effective temporal resolution of our system is improved with spatio-temporal regularisation implemented through a Kalman filtering approach, allowing us to image transient haemodynamic changes. By using this filtering technique with intensity and mean time-of-flight datatypes, we have reconstructed images of changes in absorption and reduced scattering coefficients in a dynamic 2D phantom. These results demonstrate that MONSTIR II is capable of resolving slow changes in tissue optical properties within volumes that are comparable to the preterm head. Following this verification study, we are progressing to imaging a 3D dynamic phantom as well as the neonatal brain at cot-side. Our current study involves scanning healthy babies to demonstrate the quality of recordings we are able to achieve in this challenging patient population, with the eventual goal of imaging functional activation and seizures.

Relationship between position of brain activity and change in optical density for NIR imaging

NASA Astrophysics Data System (ADS)

Kashio, Yoshihiko; Ono, Muneo; Firbank, Michael; Schweiger, Martin; Arridge, Simon R.; Okada, Eiji

2000-11-01

Multi-channel NIR system can obtain the topographic image of brain activity. Since the image is reconstructed from the change in optical density measured with the source-detector pairs, it is important to reveal the volume of tissue sampled by each source-detector pair. In this study, the light propagation in three-dimensional adult head model is calculated by hybrid radiosity-diffusion method. The model is a layered slab which mimics the extra cerebral tissue (skin, skull), CSF and brain. The change in optical density caused by the absorption change in a small cylindrical region of 10 mm in diameter at various positions in the brain is calculated. The greatest change in optical density can be observed when the absorber is located in the middle of the source and detector. When the absorber is located just below the source or detector, the change in optical density is almost half of that caused by the same absorber in the midpoint. The light propagation in the brain is strongly affected by the presence of non-scattering layer and consequently sensitive region is broadly distributed on the brain surface.

Near-infrared spectroscopy of the adult head: effect of scattering and absorbing obstructions in the cerebrospinal fluid layer on light distribution in the tissue.

PubMed

Dehghani, H; Delpy, D T

2000-09-01

Previous modeling of near-infrared (NIR) light distribution in models of the adult head incorporating a clear nonscattering cerebrospinal fluid (CSF) layer have shown the latter to have a profound effect on the resulting photon measurement density function (PMDF). In particular, the presence of the CSF limits the PMDF largely to the outer cortical gray matter with little signal contribution from the deeper white matter. In practice, the CSF is not a simple unobstructed clear layer but contains light-scattering membranes and is crossed by various blood vessels. Using a radiosity-diffusion finite-element model, we investigated the effect on the PMDF of introducing intrusions within the clear layer. The results show that the presence of such obstructions does not significantly increase the light penetration into the brain tissue, except immediately adjacent to the obstruction and that its presence also increases the light sampling of the adjacent skull tissues, which would lead to additional contamination of the NIR spectroscopy signal by the surface tissue layers.

High-refractive index of acrylate embedding resin clarifies mouse brain tissue.

PubMed

Zhou, Hongfu; Xiong, Yumiao; Wang, Yu; Wang, Xiaojun; Li, Pei; Gang, Yadong; Liu, Xiuli; Zeng, Shaoqun

2017-11-01

Biological tissue transparency combined with light-sheet fluorescence microscopy is a useful method for studying the neural structure of biological tissues. The development of light-sheet fluorescence microscopy also promotes progress in biological tissue clearing methods. The current clarifying methods mostly use liquid reagent to denature protein or remove lipids first, to eliminate or reduce the scattering index or refractive index of the biological tissue. However, denaturing protein and removing lipids require complex procedures or an extended time period. Therefore, here we have developed acrylate resin with a high refractive index, which causes clearing of biological tissue directly after polymerization. This method can improve endogenous fluorescence retention by adjusting the pH value of the resin monomer. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

A versatile new technique to clear mouse and human brain

NASA Astrophysics Data System (ADS)

Costantini, Irene; Di Giovanna, Antonino Paolo; Allegra Mascaro, Anna Letizia; Silvestri, Ludovico; Müllenbroich, Marie Caroline; Sacconi, Leonardo; Pavone, Francesco S.

2015-07-01

Large volumes imaging with microscopic resolution is limited by light scattering. In the last few years based on refractive index matching, different clearing approaches have been developed. Organic solvents and water-based optical clearing agents have been used for optical clearing of entire mouse brain. Although these methods guarantee high transparency and preservation of the fluorescence, though present other non-negligible limitations. Tissue transformation by CLARITY allows high transparency, whole brain immunolabelling and structural and molecular preservation. This method however requires a highly expensive refractive index matching solution limiting practical applicability. In this work we investigate the effectiveness of a water-soluble clearing agent, the 2,2'-thiodiethanol (TDE) to clear mouse and human brain. TDE does not quench the fluorescence signal, is compatible with immunostaining and does not introduce any deformation at sub-cellular level. The not viscous nature of the TDE make it a suitable agent to perform brain slicing during serial two-photon (STP) tomography. In fact, by improving penetration depth it reduces tissue slicing, decreasing the acquisition time and cutting artefacts. TDE can also be used as a refractive index medium for CLARITY. The potential of this method has been explored by imaging a whole transgenic mouse brain with the light sheet microscope. Moreover we apply this technique also on blocks of dysplastic human brain tissue transformed with CLARITY and labeled with different antibody. This clearing approach significantly expands the application of single and two-photon imaging, providing a new useful method for quantitative morphological analysis of structure in mouse and human brain.

Use of diffuse optical spectroscopy to monitor muscle and brain oxygenation dynamics during isometric and isokinetic exercise

NASA Astrophysics Data System (ADS)

Ganesan, Goutham; Cotter, Joshua; Reuland, Warren; Warren, Robert V.; Mirzaei Zarandi, Soroush M.; Cerussi, Albert E.; Tromberg, Bruce J.; Galassetti, Pietro

2013-03-01

The use of near-infrared time-resolved spectroscopy (TRS-20, Hamamatsu Corporation) in two resistance type exercise applications in human subjects is described. First, using isometric flexion of the biceps, we compared the magnitude and relevance of tissue hemoglobin concentration and oxygen saturation (stO2) changes when assuming constant scattering versus continuous measurement of reduced scattering coefficients at three wavelengths. It was found that the assumption of constant scattering resulted in significant errors in hemoglobin concentration assessment during sustained isometric contractions. Secondly, we tested the effect of blood flow restriction (BFR) on oxygenation in a muscle (vastus medialis oblique, VMO) and in the prefrontal cortex (PFC) of the brain. The BFR training technique resulted in considerably more fatigability in subjects, and correlated with reduced muscle stO2 between sets of exertion. Additionally, exercise with BFR resulted in greater PFC deoxygenation than a condition with equivalent work performance but no BFR. These experiments demonstrate novel applications for diffuse optical spectroscopy in strength testing and targeted muscle rehabilitation.

Study the efficacy of neuroprotective drugs on brain physiological properties during focal head injury using optical spectroscopy data analysis

NASA Astrophysics Data System (ADS)

Abookasis, David; Shochat, Ariel

2016-03-01

We present a comparative evaluation of five different neuroprotective drugs in the early phase following focal traumatic brain injury (TBI) in mouse intact head. The effectiveness of these drugs in terms of changes in brain tissue morphology and hemodynamic properties was experimentally evaluated through analysis of the optical absorption coefficient and spectral reduced scattering parameters in the range of 650-1000 nm. Anesthetized male mice (n=50 and n=10 control) were subjected to weight drop model mimics real life focal head trauma. Monitoring the effect of injury and neuroprotective drugs was obtained by using a diffuse reflectance spectroscopy system utilizing independent source-detector separation and location. Result indicates that administration of minocycline improve hemodynamic and reduced the level of tissue injury at an early phase post-injury while hypertonic saline treatment decrease brain water content. These findings highlight the heterogeneity between neuroprotective drugs and the ongoing controversy among researchers regarding which drug therapy is preferred for treatment of TBI. On the other hand, our results show the capability of optical spectroscopy technique to noninvasively study brain function following injury and drug therapy.

Modeling of light distribution in the brain for topographical imaging

NASA Astrophysics Data System (ADS)

Okada, Eiji; Hayashi, Toshiyuki; Kawaguchi, Hiroshi

2004-07-01

Multi-channel optical imaging system can obtain a topographical distribution of the activated region in the brain cortex by a simple mapping algorithm. Near-infrared light is strongly scattered in the head and the volume of tissue that contributes to the change in the optical signal detected with source-detector pair on the head surface is broadly distributed in the brain. This scattering effect results in poor resolution and contrast in the topographic image of the brain activity. We report theoretical investigations on the spatial resolution of the topographic imaging of the brain activity. The head model for the theoretical study consists of five layers that imitate the scalp, skull, subarachnoid space, gray matter and white matter. The light propagation in the head model is predicted by Monte Carlo simulation to obtain the spatial sensitivity profile for a source-detector pair. The source-detector pairs are one dimensionally arranged on the surface of the model and the distance between the adjoining source-detector pairs are varied from 4 mm to 32 mm. The change in detected intensity caused by the absorption change is obtained by Monte Carlo simulation. The position of absorption change is reconstructed by the conventional mapping algorithm and the reconstruction algorithm using the spatial sensitivity profiles. We discuss the effective interval between the source-detector pairs and the choice of reconstruction algorithms to improve the topographic images of brain activity.

Spectroscopic method for determination of the absorption coefficient in brain tissue

NASA Astrophysics Data System (ADS)

Johansson, Johannes D.

2010-09-01

I use Monte Carlo simulations and phantom measurements to characterize a probe with adjacent optical fibres for diffuse reflectance spectroscopy during stereotactic surgery in the brain. Simulations and measurements have been fitted to a modified Beer-Lambert model for light transport in order to be able to quantify chromophore content based on clinically measured spectra in brain tissue. It was found that it is important to take the impact of the light absorption into account when calculating the apparent optical path length, lp, for the photons in order to get good estimates of the absorption coefficient, μa. The optical path length was found to be well fitted to the equation lp=a+b ln(Is)+c ln(μa)+d ln(Is)ln(μa), where Is is the reflected light intensity for scattering alone (i.e., zero absorption). Although coefficients a-d calculated in this study are specific to the probe used here, the general form of the equation should be applicable to similar probes.

Resonance Raman Spectroscopy of human brain metastasis of lung cancer analyzed by blind source separation

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-Hui; Pu, Yang; Cheng, Gangge; Yu, Xinguang; Zhou, Lixin; Lin, Dongmei; Zhu, Ke; Alfano, Robert R.

2017-02-01

Resonance Raman (RR) spectroscopy offers a novel Optical Biopsy method in cancer discrimination by a means of enhancement in Raman scattering. It is widely acknowledged that the RR spectrum of tissue is a superposition of spectra of various key building block molecules. In this study, the Resonance Raman (RR) spectra of human metastasis of lung cancerous and normal brain tissues excited by a visible selected wavelength at 532 nm are used to explore spectral changes caused by the tumor evolution. The potential application of RR spectra human brain metastasis of lung cancer was investigated by Blind Source Separation such as Principal Component Analysis (PCA). PCA is a statistical procedure that uses an orthogonal transformation to convert a set of observations of possibly correlated variables into a set of values of linearly uncorrelated variables called principal components (PCs). The results show significant RR spectra difference between human metastasis of lung cancerous and normal brain tissues analyzed by PCA. To evaluate the efficacy of for cancer detection, a linear discriminant analysis (LDA) classifier is utilized to calculate the sensitivity, and specificity and the receiver operating characteristic (ROC) curves are used to evaluate the performance of this criterion. Excellent sensitivity of 0.97, specificity (close to 1.00) and the Area Under ROC Curve (AUC) of 0.99 values are achieved under best optimal circumstance. This research demonstrates that RR spectroscopy is effective for detecting changes of tissues due to the development of brain metastasis of lung cancer. RR spectroscopy analyzed by blind source separation may have potential to be a new armamentarium.

Nonlinear adaptive optics: aberration correction in three photon fluorescence microscopy for mouse brain imaging

NASA Astrophysics Data System (ADS)

Sinefeld, David; Paudel, Hari P.; Wang, Tianyu; Wang, Mengran; Ouzounov, Dimitre G.; Bifano, Thomas G.; Xu, Chris

2017-02-01

Multiphoton fluorescence microscopy is a well-established technique for deep-tissue imaging with subcellular resolution. Three-photon microscopy (3PM) when combined with long wavelength excitation was shown to allow deeper imaging than two-photon microscopy (2PM) in biological tissues, such as mouse brain, because out-of-focus background light can be further reduced due to the higher order nonlinear excitation. As was demonstrated in 2PM systems, imaging depth and resolution can be improved by aberration correction using adaptive optics (AO) techniques which are based on shaping the scanning beam using a spatial light modulator (SLM). In this way, it is possible to compensate for tissue low order aberration and to some extent, to compensate for tissue scattering. Here, we present a 3PM AO microscopy system for brain imaging. Soliton self-frequency shift is used to create a femtosecond source at 1675 nm and a microelectromechanical (MEMS) SLM serves as the wavefront shaping device. We perturb the 1020 segment SLM using a modified nonlinear version of three-point phase shifting interferometry. The nonlinearity of the fluorescence signal used for feedback ensures that the signal is increasing when the spot size decreases, allowing compensation of phase errors in an iterative optimization process without direct phase measurement. We compare the performance for different orders of nonlinear feedback, showing an exponential growth in signal improvement as the nonlinear order increases. We demonstrate the impact of the method by applying the 3PM AO system for in-vivo mouse brain imaging, showing improvement in signal at 1-mm depth inside the brain.

Spatial frequency domain tomography of protoporphyrin IX fluorescence in preclinical glioma models

PubMed Central

Konecky, Soren D.; Owen, Chris M.; Rice, Tyler; Valdés, Pablo A.; Kolste, Kolbein; Wilson, Brian C.; Leblond, Frederic; Roberts, David W.; Paulsen, Keith D.

2012-01-01

Abstract. Multifrequency (0 to 0.3  mm−1), multiwavelength (633, 680, 720, 800, and 820 nm) spatial frequency domain imaging (SFDI) of 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) was used to recover absorption, scattering, and fluorescence properties of glioblastoma multiforme spheroids in tissue-simulating phantoms and in vivo in a mouse model. Three-dimensional tomographic reconstructions of the frequency-dependent remitted light localized the depths of the spheroids within 500 μm, and the total amount of PpIX in the reconstructed images was constant to within 30% when spheroid depth was varied. In vivo tumor-to-normal contrast was greater than ∼1.5 in reduced scattering coefficient for all wavelengths and was ∼1.3 for the tissue concentration of deoxyhemoglobin (ctHb). The study demonstrates the feasibility of SFDI for providing enhanced image guidance during surgical resection of brain tumors. PMID:22612131

Functional imaging of small tissue volumes with diffuse optical tomography

NASA Astrophysics Data System (ADS)

Klose, Alexander D.; Hielscher, Andreas H.

2006-03-01

Imaging of dynamic changes in blood parameters, functional brain imaging, and tumor imaging are the most advanced application areas of diffuse optical tomography (DOT). When dealing with the image reconstruction problem one is faced with the fact that near-infrared photons, unlike X-rays, are highly scattered when they traverse biological tissue. Image reconstruction schemes are required that model the light propagation inside biological tissue and predict measurements on the tissue surface. By iteratively changing the tissue-parameters until the predictions agree with the real measurements, a spatial distribution of optical properties inside the tissue is found. The optical properties can be related to the tissue oxygenation, inflammation, or to the fluorophore concentration of a biochemical marker. If the model of light propagation is inaccurate, the reconstruction process will lead to an inaccurate result as well. Here, we focus on difficulties that are encountered when DOT is employed for functional imaging of small tissue volumes, for example, in cancer studies involving small animals, or human finger joints for early diagnosis of rheumatoid arthritis. Most of the currently employed image reconstruction methods rely on the diffusion theory that is an approximation to the equation of radiative transfer. But, in the cases of small tissue volumes and tissues that contain low scattering regions diffusion theory has been shown to be of limited applicability Therefore, we employ a light propagation model that is based on the equation of radiative transfer, which promises to overcome the limitations.

Scattering properties of normal and cancerous tissues from human stomach based on phase-contrast microscope

NASA Astrophysics Data System (ADS)

Zhang, Hui; Li, Zhifang; Li, Hui

2012-12-01

In order to study scattering properties of normal and cancerous tissues from human stomach, we collect images for human gastric specimens by using phase-contrast microscope. The images were processed by the way of mathematics morphology. The equivalent particle size distribution of tissues can be obtained. Combining with Mie scattering theory, the scattering properties of tissues can be calculated. Assume scattering of light in biological tissue can be seen as separate scattering events by different particles, total scattering properties can be equivalent to as scattering sum of particles with different diameters. The results suggest that scattering coefficient of the cancerous tissue is significantly higher than that of normal tissue. The scattering phase function is different especially in the backscattering area. Those are significant clinical benefits to diagnosis cancerous tissue

Spatial localization and temporal analysis of optical property fluctuations by multiplexed near-infrared photon density waves in turbid media: In vitro and in vivo studies

NASA Astrophysics Data System (ADS)

Filiaci, Mattia Emidio

2001-12-01

In recent years the application of near infrared non- invasive methods for medical diagnostics and clinical studies has grown rapidly. The ease of use, low cost and portability of these methods is a clear advantage over other techniques such as MRI. The limitations in detection of optical property inhomogeneities in tissues, such as tumors or hematomas, is due to the diffusive, highly scattering nature of near infrared light propagation. I have studied and developed methods to improve the spatial localization of these inhomogeneities in biological tissues, especially for the application of functional studies of the human brain in vivo. Recently much attention has been given to the study of the processes in the human brain that lead to the changing of the optical parameters that characterize the tissue, measured by our frequency-domain instrumentation. These processes have been divided into two main categories with different time-scales. The slower one is mostly due to the fluctuations in the absorption coefficient caused by oxy- and deoxy-hemoglobin changes in the tissue. The temporal analysis of the signal resulting from this process is studied in detail, and I also introduce a time-series data analysis technique that has not been applied to this field before but was introduced in another area very recently. The faster time-scale process has been attributed to the electrochemical excitation of the individual neurons in the brain that have been observed to cause a change in the scattering coefficient of the tissue. This is the other primary parameter that is measured by our frequency domain instrument. However, before this work it has not been clear how to go about to better localize these smaller fluctuations. I present a novel idea for improving spatial localization of macroscopic optical parameter fluctuations, and study the characteristics of this optical probe design using analytical solutions to the diffusion equation and Monte Carlo simulations that more appropriately represent the volume of excitation of the cortex neurons.

Time-reversed ultrasonically encoded (TRUE) focusing for deep-tissue optogenetic modulation

NASA Astrophysics Data System (ADS)

Brake, Joshua; Ruan, Haowen; Robinson, J. Elliott; Liu, Yan; Gradinaru, Viviana; Yang, Changhuei

2018-02-01

The problem of optical scattering was long thought to fundamentally limit the depth at which light could be focused through turbid media such as fog or biological tissue. However, recent work in the field of wavefront shaping has demonstrated that by properly shaping the input light field, light can be noninvasively focused to desired locations deep inside scattering media. This has led to the development of several new techniques which have the potential to enhance the capabilities of existing optical tools in biomedicine. Unfortunately, extending these methods to living tissue has a number of challenges related to the requirements for noninvasive guidestar operation, speed, and focusing fidelity. Of existing wavefront shaping methods, time-reversed ultrasonically encoded (TRUE) focusing is well suited for applications in living tissue since it uses ultrasound as a guidestar which enables noninvasive operation and provides compatibility with optical phase conjugation for high-speed operation. In this paper, we will discuss the results of our recent work to apply TRUE focusing for optogenetic modulation, which enables enhanced optogenetic stimulation deep in tissue with a 4-fold spatial resolution improvement in 800-micron thick acute brain slices compared to conventional focusing, and summarize future directions to further extend the impact of wavefront shaping technologies in biomedicine.

Methodology and apparatus for diffuse photon imaging

DOEpatents

Feng, S.C.; Zeng, F.; Zhao, H.L.

1997-12-09

Non-invasive near infrared optical medical imaging devices for both hematoma detection in the brain and early tumor detection in the breast is achieved using image reconstruction which allows a mapping of the position dependent contrast diffusive propagation constants, which are related to the optical absorption coefficient and scattering coefficient in the tissue, at near infrared wavelengths. Spatial resolutions in the range of 5 mm for adult brain sizes and breast sizes can be achieved. The image reconstruction utilizes WKB approximation on most probable diffusion paths which has as lowest order approximation the straight line-of-sight between the plurality of sources and the plurality of detectors. The WKB approximation yields a set of linear equations in which the contrast optical absorption coefficients are the unknowns and for which signals can be generated to produce a pixel map of the contrast optical resolution of the scanned tissue. 58 figs.

Methodology and apparatus for diffuse photon mimaging

DOEpatents

Feng, Shechao C.; Zeng, Fanan; Zhao, Hui-Lin

1997-12-09

Non-invasive near infrared optical medical imaging devices for both hematoma detection in the brain and early tumor detection in the breast is achieved using image reconstruction which allows a mapping of the position dependent contrast diffusive propagation constants, which are related to the optical absorption coefficient and scattering coefficient in the tissue, at near infrared wavelengths. Spatial resolutions in the range of 5 mm for adult brain sizes and breast sizes can be achieved. The image reconstruction utilizes WKB approximation on most probable diffusion paths which has as lowest order approximation the straight line-of-sight between the plurality of sources and the plurality of detectors. The WKB approximation yields a set of linear equations in which the contrast optical absorption coefficients are the unknowns and for which signals can be generated to produce a pixel map of the contrast optical resolution of the scanned tissue.

Investigation of scattering coefficients and anisotropy factors of human cancerous and normal prostate tissues using Mie theory

NASA Astrophysics Data System (ADS)

Pu, Yang; Chen, Jun; Wang, Wubao

2014-02-01

The scattering coefficient, μs, the anisotropy factor, g, the scattering phase function, p(θ), and the angular dependence of scattering intensity distributions of human cancerous and normal prostate tissues were systematically investigated as a function of wavelength, scattering angle and scattering particle size using Mie theory and experimental parameters. The Matlab-based codes using Mie theory for both spherical and cylindrical models were developed and applied for studying the light propagation and the key scattering properties of the prostate tissues. The optical and structural parameters of tissue such as the index of refraction of cytoplasm, size of nuclei, and the diameter of the nucleoli for cancerous and normal human prostate tissues obtained from the previous biological, biomedical and bio-optic studies were used for Mie theory simulation and calculation. The wavelength dependence of scattering coefficient and anisotropy factor were investigated in the wide spectral range from 300 nm to 1200 nm. The scattering particle size dependence of μs, g, and scattering angular distributions were studied for cancerous and normal prostate tissues. The results show that cancerous prostate tissue containing larger size scattering particles has more contribution to the forward scattering in comparison with the normal prostate tissue. In addition to the conventional simulation model that approximately considers the scattering particle as sphere, the cylinder model which is more suitable for fiber-like tissue frame components such as collagen and elastin was used for developing a computation code to study angular dependence of scattering in prostate tissues. To the best of our knowledge, this is the first study to deal with both spherical and cylindrical scattering particles in prostate tissues.

Development and characterization of non-resonant multiphoton photoacoustic spectroscopy (NMPPAS) for brain tumor margining

NASA Astrophysics Data System (ADS)

Dahal, Sudhir

During tumor removal surgery, due to the problems associated with obtaining high-resolution, real-time chemical images of where exactly the tumor ends and healthy tissue begins (tumor margining), it is often necessary to remove a much larger volume of tissue than the tumor itself. In the case of brain tumor surgery, however, it is extremely unsafe to remove excess tissue. Therefore, without an accurate image of the tumor margins, some of the tumor's finger-like projections are inevitably left behind in the surrounding parenchyma to grow again. For this reason, the development of techniques capable of providing high-resolution real-time images of tumor margins up to centimeters below the surface of a tissue is ideal for the diagnosis and treatment of tumors, as well as surgical guidance during brain tumor excision. A novel spectroscopic technique, non-resonant multiphoton photoacoustic spectroscopy (NMPPAS), is being developed with the capabilities of obtaining high-resolution subsurface chemical-based images of underlying tumors. This novel technique combines the strengths of multiphoton tissue spectroscopy and photoacoustic spectroscopy into a diagnostic methodology that will, ultimately, provide unparalleled chemical information and images to provide the state of sub-surface tissues. The NMPPAS technique employs near-infrared light (in the diagnostic window) to excite ultraviolet and/or visible light absorbing species deep below the tissue's surface. Once a multiphoton absorption event occurs, non-radiative relaxation processes generates a localized thermal expansion and subsequent acoustic wave that can be detected using a piezoelectric transducer. Since NMPPAS employs an acoustic detection modality, much deeper diagnoses can be performed than that is possible using current state of the art high-resolution chemical imaging techniques such as multiphoton fluorescence spectroscopy. NMPPAS was employed to differentiate between excised brain tumors (astrocytoma III) and healthy tissue with over 99% accuracy. NMPPAS spectral features showed evident differences between tumor and healthy tissues, and ratiometric analysis ensured that only a few wavelengths could be used for excitation instead of using numerous wavelength excitations to create spectra. This process would significantly reduce the analysis time while maintaining the same degree of accuracy. Tissue phantoms were fabricated in order to characterize the properties of NMPPAS. Scattering particles were doped into the phantoms to simulate their light scattering properties to real tissues. This allowed for better control over shape, size, reproducibility and doping in the sample while maintaining the light-tissue interaction properties of real tissue. To make NMPPAS viable for clinical applications, the technique was characterized to determine the spatial (lateral and longitudinal) resolution, depth of penetration and its ability to image in three-dimension through layers of tissue. Both resolutions were determined to be near-cellular level resolution (50-70 microm), obtained initially with the aid of the technique of multiphoton fluorescence, and later verified using NMPPAS imaging. Additionally, the maximum depth of penetration and detection was determined to be about 1.4cm, making the technique extremely suitable to margin tumors from underlying tissues in the brain. The capability of NMPPAS to detect and image layers that lie beneath other structures and blood vessels was also investigated. Three-dimensional images were obtained for the first time using NMPPAS. The images were obtained from different depths and structures were imaged through other layers of existing structures in the sample. This verified that NMPPAS was capable of detecting and imaging structures that lie embedded within the tissues. NMPPAS images of embedded structures were also obtained with the presence of hemoglobin, which is potentially the largest source of background in blood-perfused tissues, thus showing that the technique is capable of detecting and differentiating in blood-perfused samples.

Far-red to near infrared emission and scattering spectroscopy for biomedical applications

NASA Astrophysics Data System (ADS)

Zhang, Gang

2001-06-01

The thesis investigates the far-red and near infrared (NIR) spectral region from biomedical tissue samples for monitoring the state of tissues. The NIR emission wing intensity is weak in comparison to the emission in the visible spectral region. The wing emission from biomedical samples has revealed meaningful information about the state of the tissues. A model is presented to explain the shape of the spectral wing based on a continuum of energy levels. The wing can be used to classify different kinds of tissues; especially it can be used to differentiate cancer part from normal human breast tissues. The research work of the far-red emission from thermal damaged tissue samples shows that the emission intensity in this spectral region is proportional to the extent of the thermal damage of the tissue. Near infrared spectral absorption method is used to investigate blood hemodynamics (perfusion and oxygenation) in brain during sleep-wake transition. The result of the research demonstrates that the continuous wave (CW) type near infrared spectroscopy (NIRS) device can be used to investigate brain blood perfusion and oxygenation with a similar precision with frequency domain (FD) type device. The human subject sleep and wake transition, has been monitored by CW type NIRS instrument with traditional electroencephalograph (EEG) method. Parallel change in oxy-Hb and deoxy-Hb is a discrete event that occurs in the transition from both sleep to wakefulness and wakefulness to sleep. These hemodynamic switches are generally about few seconds delayed from the human decided transition point between sleep and wake on the polygraph EEG recording paper. The combination of NIRS and EEG methods monitor the brain activity, gives more information about the brain activity. The sleep apnea investigation was associated with recurrent apneas, insufficient nasal continuous positive airway pressure (CPAP) and the different response of the peripheral and central compartments to breathing events. The different results with finger pulse oximetry and NIRS suggest that optical monitoring of the brain may have advantages that may help clarify the morbidity of obstructive sleep apnea (OSA) Syndrome.

Diffuse near-infrared reflectance spectroscopy during heatstroke in a mouse model: pilot study.

PubMed

Abookasis, David; Zafrir, Elad; Nesher, Elimelech; Pinhasov, Albert; Sternklar, Shmuel; Mathews, Marlon S

2012-10-01

Heatstroke, a form of hyperthermia, is a life-threatening condition characterized by an elevated core body temperature that rises above 40°C (104°F) and central nervous system dysfunction that results in delirium, convulsions, or coma. Without emergency treatment, the victim lapses into a coma and death soon follows. The study presented was conducted with a diffuse reflectance spectroscopy (DRS) setup to assess the effects of brain dysfunction that occurred during heatstroke in mice model (n=6). It was hypothesized that DRS can be utilized in small animal studies to monitor change in internal brain tissue temperature during heatstroke injury since it induces a sequence of pathologic changes that change the tissue composition and structure. Heatstroke was induced by exposure of the mice body under general anesthesia, to a high ambient temperature. A type of DRS in which the brain tissue was illuminated through the intact scalp with a broadband light source and diffuse reflected spectra was employed, taking in the spectral region between 650 and 1000 nm and acquired at an angle of 90 deg at a position on the scalp ∼12  mm from the illumination site. The temperature at the onset of the experiment was ∼34°C (rectal temperature) with increasing intervals of 1°C until mouse death. The increase in temperature caused optical scattering signal changes consistent with a structural alteration of brain tissue, ultimately resulting in death. We have found that the peak absorbance intensity and its second derivative at specific wavelengths correlate well with temperature with an exponential dependence. Based on these findings, in order to estimate the influence of temperature on the internal brain tissue a reflectance-temperature index was established and was seen to correlate as well with measured temperature. Overall, results indicate variations in neural tissue properties during heatstroke and the feasibility to monitor and assess internal temperature variations using DRS. Although several approaches have described the rise in temperature and its impact on tissue, to the best of our knowledge no information is available describing the ability to monitor temperature during heatstroke with DRS. The motivation of this study was to successfully describe this ability.

Hemodynamic monitoring in different cortical layers with a single fiber optical system

NASA Astrophysics Data System (ADS)

Yu, Linhui; Noor, M. Sohail; Kiss, Zelma H. T.; Murari, Kartikeya

2018-02-01

Functional monitoring of highly-localized deep brain structures is of great interest. However, due to light scattering, optical methods have limited depth penetration or can only measure from a large volume. In this research, we demonstrate continuous measurement of hemodynamics in different cortical layers in response to thalamic deep brain stimulation (DBS) using a single fiber optical system. A 200-μm-core-diameter multimode fiber is used to deliver and collect light from tissue. The fiber probe can be stereotaxically implanted into the brain region of interest at any depth to measure the di use reflectance spectra from a tissue volume of 0.02-0.03 mm3 near the fiber tip. Oxygenation is then extracted from the reflectance spectra using an algorithm based on Monte Carlo simulations. Measurements were performed on the surface (cortical layer I) and at 1.5 mm depth (cortical layer VI) of the motor cortex in anesthetized rats with thalamic DBS. Preliminary results revealed the oxygenation changes in response to DBS. Moreover, the baseline as well as the stimulus-evoked change in oxygenation were different at the two depths of cortex.

Relationship between time-resolved and non-time-resolved Beer-Lambert law in turbid media.

PubMed

Nomura, Y; Hazeki, O; Tamura, M

1997-06-01

The time-resolved Beer-Lambert law proposed for oxygen monitoring using pulsed light was extended to the non-time-resolved case in a scattered medium such as living tissues with continuous illumination. The time-resolved Beer-Lambert law was valid for the phantom model and living tissues in the visible and near-infrared regions. The absolute concentration and oxygen saturation of haemoglobin in rat brain and thigh muscle could be determined. The temporal profile of rat brain was reproduced by Monte Carlo simulation. When the temporal profiles of rat brain under different oxygenation states were integrated with time, the absorbance difference was linearly related to changes in the absorption coefficient. When the simulated profiles were integrated, there was a linear relationship within the absorption coefficient which was predicted for fractional inspiratory oxygen concentration from 10 to 100% and, in the case beyond the range of the absorption coefficient, the deviation from linearity was slight. We concluded that an optical pathlength which is independent of changes in the absorption coefficient is a good approximation for near-infrared oxygen monitoring.

Planar small-angle x-ray scattering imaging of phantoms and biological samples

NASA Astrophysics Data System (ADS)

Choi, M.; Badano, A.

2017-04-01

Coherent small-angle x-ray scattering (SAXS) provides molecular and nanometer-scale structural information. By capturing SAXS data at multiple locations across a sample, we obtained planar images and observed improved contrast given by the difference in the material scattering cross sections. We use phantoms made with 3D printing techniques, with tissue-mimicking plastic (PMMA), and with a highly scattering reference material (AgBe), which were chosen because of their well characterized scattering cross section to demonstrate and characterize the planar imaging of a laboratory SAXS system. We measure 1.07 and 2.14 nm-1 angular intensity maps for AgBe, 9.5 nm-1 for PMMA, and 12.3 nm-1 for Veroclear. The planar SAXS images show material discrimination based on their cross sectional features. The image signal-to-noise ratio (SNR) of each q image was dependent on exposure time and x-ray flux. We observed a lower SNR (91 ± 48) at q angles where no characteristic peaks for either material exist. To improve the visualization of the acquired data by utilizing all q-binned data, we describe a weighted-sum presentation method with a priori knowledge of relevant cross sections to improve the SNR (10 000 ± 6400) over the SNR from a single q-image at 1.07 nm-1 (1100 ± 620). In addition, we describe planar SAXS imaging of a mouse brain slice showing differentiation of tissue types as compared to a conventional absorption-based x-ray imaging technique.

Development of a multi-exposure speckle imaging for mice brain imaging

NASA Astrophysics Data System (ADS)

Soleimanzad, Haleh; Gurden, Hirac; Pain, Frédéric

2017-02-01

In the last decade, Laser Speckle Contrast Imaging (LSCI) has been proposed and validated for imaging cerebral blood flow at the rodent brain surface in vivo. The technique relies on the calculation of the spatial speckle contrast, which is related to the velocity of scatterers (red blood cells). The implementation of the technique requires a partial craniotomy so that the brain tissues of interest can be illuminated with a laser diode. However, the studies of changes in the microcirculation during disease progression or treatment require longitudinal studies (i.e. imaging is done repeatedly over weeks or even months). Practically, the less invasive way to obtain such data is to image through the thinned skull without a craniotomy. However the presence of static scatterers (skull) will affect the speckle calculation and produce a bias in the estimation of the microcirculation changes. An extension to LSCI, termed Multi-Exposure Speckle Imaging (MESI) was proposed and validated a few years ago that address these limitations. It relies on a model of the speckle contrast as a function of the exposure time and the proportion of static scatterers. Here, we used MESI with the aim of repeatedly imaging the olfactory bulb of mice models of obesity. First, we have developed a MESI set up which was characterized on microfluidic flow phantoms with different flow-rates and channel diameters to simulate blood flow in animal model characteristics. Second, we show that MESI can discriminate flows in the presence of static scatterers and it can measure flow changes consistently. Finally we provide an in vivo validation of the technique in mice with and without a craniotomy.

Hemodynamic measurements in rat brain and human muscle using diffuse near-infrared absorption and correlation spectroscopies

NASA Astrophysics Data System (ADS)

Yu, Guoqiang; Durduran, Turgut; Furuya, D.; Lech, G.; Zhou, Chao; Chance, Britten; Greenberg, J. H.; Yodh, Arjun G.

2003-07-01

Measurement of concentration, oxygenation, and flow characteristics of blood cells can reveal information about tissue metabolism and functional heterogeneity. An improved multifunctional hybrid system has been built on the basis of our previous hybrid instrument that combines two near-infrared diffuse optical techniques to simultaneously monitor the changes of blood flow, total hemoglobin concentration (THC) and blood oxygen saturation (StO2). Diffuse correlation spectroscopy (DCS) monitors blood flow (BF) by measuring the optical phase shifts caused by moving blood cells, while diffuse photon density wave spectroscopy (DPDW) measures tissue absorption and scattering. Higher spatial resolution, higher data acquisition rate and higher dynamic range of the improved system allow us to monitor rapid hemodynamic changes in rat brain and human muscles. We have designed two probes with different source-detector pairs and different separations for the two types of experiments. A unique non-contact probe mounted on the back of a camera, which allows continuous measurements without altering the blood flow, was employed to in vivo monitor the metabolic responses in rat brain during KCl induced cortical spreading depression (CSD). A contact probe was used to measure changes of blood flow and oxygenation in human muscle during and after cuff occlusion or exercise, where the non-contact probe is not appropriate for monitoring the moving target. The experimental results indicate that our multifunctional hybrid system is capable of in vivo and non-invasive monitoring of the hemodynamic changes in different tissues (smaller tissues in rat brain, larger tissues in human muscle) under different conditions (static versus moving). The time series images of flow during CSD obtained by our technique revealed spatial and temporal hemodynamic changes in rat brain. Two to three fold longer recovery times of flow and oxygenation after cuff occlusion or exercise from calf flexors in a patient with peripheral vascular disease (PVD) were found.

Localized cortical chronic traumatic encephalopathy pathology after single, severe axonal injury in human brain.

PubMed

Shively, Sharon B; Edgerton, Sarah L; Iacono, Diego; Purohit, Dushyant P; Qu, Bao-Xi; Haroutunian, Vahram; Davis, Kenneth L; Diaz-Arrastia, Ramon; Perl, Daniel P

2017-03-01

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangles), astrocytes and cell processes distributed around small blood vessels at sulcal depths in irregular patterns within the cortex. The pathophysiological mechanism for this lesion is unknown. Moreover, a subset of CTE cases harbors cortical β-amyloid plaques. In this study, we analyzed postmortem brain tissues from five institutionalized patients with schizophrenia and history of surgical leucotomy with subsequent survival of at least another 40 years. Because leucotomy involves severing axons bilaterally in prefrontal cortex, this surgical procedure represents a human model of single traumatic brain injury with severe axonal damage and no external impact. We examined cortical tissues at the leucotomy site and at both prefrontal cortex rostral and frontal cortex caudal to the leucotomy site. For comparison, we analyzed brain tissues at equivalent neuroanatomical sites from non-leucotomized patients with schizophrenia, matched in age and gender. All five leucotomy cases revealed severe white matter damage with dense astrogliosis at the axotomy site and also neurofibrillary tangles and p-tau immunoreactive neurites in the overlying gray matter. Four cases displayed p-tau immunoreactivity in neurons, astrocytes and cell processes encompassing blood vessels at cortical sulcal depths in irregular patterns, similar to CTE. The three cases with apolipoprotein E ε4 haplotype showed scattered β-amyloid plaques in the overlying gray matter, but not the two cases with apolipoprotein E ε3/3 genotype. Brain tissue samples from prefrontal cortex rostral and frontal cortex caudal to the leucotomy site, and all cortical samples from the non-leucotomized patients, showed minimal p-tau and β-amyloid pathology. These findings suggest that chronic axonal damage contributes to the unique pathology of CTE over time.

Phase-resolved reflectance spectroscopy on layered turbid media

NASA Astrophysics Data System (ADS)

Hielscher, Andreas H.; Liu, Hanli; Chance, Britton; Tittel, Frank K.; Jacques, Steven L.

1995-05-01

In this study, we investigate the influence of layered tissue structures on the phase-resolved reflectance. As a particular example, we consider the affect of the skin, skull, and meninges on noninvasive blood oxygenation determination of the brain. In this case, it's important to know how accurate one can measure the absorption coefficient of the brain through the enclosing layers of different tissues. Experiments were performed on layered gelatin tissue phantoms and the results compared to diffusion theory. It is shown that when a high absorbing medium is placed on top of a low absorbing medium, the absorption coefficient of the lower layer is accessible. In the inverse case, where a low absorbing medium is placed on top of a high absorbing medium, the absorption coefficient of the underlying medium can only be determined if the differences in the absorption coefficient are small, or the top layer is very thin. Investigations on almost absorption and scattering free layers, like the cerebral fluid filled arachnoid, reveal that the determination of the absorption coefficient is barely affected by these kinds of structures.

SU-D-207A-02: Possible Characterization of the Brain Tumor Vascular Environment by a Novel Strategy of Quantitative Analysis in Dynamic Contrast Enhanced MR Imaging: A Combination of Both Patlak and Logan Analyses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yee, S; Chinnaiyan, P; Wloch, J

Purpose: The majority of quantitative analyses involving dynamic contrast enhanced (DCE) MRI have been performed to obtain kinetic parameters such as Ktrans and ve. Such analyses are generally performed assuming a “reversible” tissue compartment, where the tracer is assumed to be rapidly equilibrated between the plasma and tissue compartments. However, some tumor vascular environments may be more suited for a “non-reversible” tissue compartment, where, as with FDG PET imaging, the tracer is continuously deposited into the tissue compartment (or the return back to the plasma compartment is very slow in the imaging time scale). Therefore, Patlak and Logan analyses, whichmore » represent tools for the “non-reversible” and “reversible” modeling, respectively, were performed to better characterize the brain tumor vascular environment. Methods: A voxel-by-voxel analysis was performed to generate both Patlak and Logan plots in two brain tumor patients, one with grade III astrocytoma and the other with grade IV astrocytoma or glioblastoma. The slopes of plots and the r-square were then obtained by linear fitting and compared for each voxel. Results: The 2-dimensional scatter plots of Logan (Y-axis) vs. Patlak slopes (X-axis) clearly showed increased Logan slopes for glioblastoma (Figure 3A). The scatter plots of goodness-of-fit (Figure 3B) also suggested glioblastoma, relative to grade III astrocytoma, might consist of more voxels that are kinetically Logan-like (i.e. rapidly equilibrated extravascular space and active vascular environment). Therefore, the enhanced Logan-like behavior (and the Logan slope) in glioblastoma may imply an increased fraction of active vascular environment, while the enhanced Patlak-like behavior implies the vascular environment permitting a relatively slower washout of the tracer. Conclusion: Although further verification is required, the combination of Patlak and Logan analyses in DCE MRI may be useful in characterizing the tumor vascular environment, and thus, may have implications in tumor grading and monitoring response to anti-vascular therapy.« less

Label-Free Delineation of Brain Tumors by Coherent Anti-Stokes Raman Scattering Microscopy in an Orthotopic Mouse Model and Human Glioblastoma

PubMed Central

Tamosaityte, Sandra; Leipnitz, Elke; Geiger, Kathrin D.; Schackert, Gabriele; Koch, Edmund; Steiner, Gerald; Kirsch, Matthias

2014-01-01

Background Coherent anti-Stokes Raman scattering (CARS) microscopy provides fine resolution imaging and displays morphochemical properties of unstained tissue. Here, we evaluated this technique to delineate and identify brain tumors. Methods Different human tumors (glioblastoma, brain metastases of melanoma and breast cancer) were induced in an orthotopic mouse model. Cryosections were investigated by CARS imaging tuned to probe C-H molecular vibrations, thereby addressing the lipid content of the sample. Raman microspectroscopy was used as reference. Histopathology provided information about the tumor's localization, cell proliferation and vascularization. Results The morphochemical contrast of CARS images enabled identifying brain tumors irrespective of the tumor type and properties: All tumors were characterized by a lower CARS signal intensity than the normal parenchyma. On this basis, tumor borders and infiltrations could be identified with cellular resolution. Quantitative analysis revealed that the tumor-related reduction of CARS signal intensity was more pronounced in glioblastoma than in metastases. Raman spectroscopy enabled relating the CARS intensity variation to the decline of total lipid content in the tumors. The analysis of the immunohistochemical stainings revealed no correlation between tumor-induced cytological changes and the extent of CARS signal intensity reductions. The results were confirmed on samples of human glioblastoma. Conclusions CARS imaging enables label-free, rapid and objective identification of primary and secondary brain tumors. Therefore, it is a potential tool for diagnostic neuropathology as well as for intraoperative tumor delineation. PMID:25198698

[Analysis of scatterer microstructure feature based on Chirp-Z transform cepstrum].

PubMed

Guo, Jianzhong; Lin, Shuyu

2007-12-01

The fundamental research field of medical ultrasound has been the characterization of tissue scatterers. The signal processing method is widely used in this research field. A new method of Chirp-Z Transform Cepstrum for mean spacing estimation of tissue scatterers using ultrasonic scattered signals has been developed. By using this method together with conventional AR cepstrum method, we processed the backscattered signals of mimic tissue and pig liver in vitro. The results illustrated that the Chirp-Z Transform Cepstrum method is effective for signal analysis of ultrasonic scattering and characterization of tissue scatterers, and it can improve the resolution for mean spacing estimation of tissue scatterers.

Vibrational imaging of glucose uptake activity in live cells and tissues by stimulated Raman scattering microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hu, Fanghao; Chen, Zhixing; Zhang, Luyuan; Shen, Yihui; Wei, Lu; Min, Wei

2016-03-01

Glucose is consumed as an energy source by virtually all living organisms, from bacteria to humans. Its uptake activity closely reflects the cellular metabolic status in various pathophysiological transformations, such as diabetes and cancer. Extensive efforts such as positron emission tomography, magnetic resonance imaging and fluorescence microscopy have been made to specifically image glucose uptake activity but all with technical limitations. Here, we report a new platform to visualize glucose uptake activity in live cells and tissues with subcellular resolution and minimal perturbation. A novel glucose analogue with a small alkyne tag (carbon-carbon triple bond) is developed to mimic natural glucose for cellular uptake, which can be imaged with high sensitivity and specificity by targeting the strong and characteristic alkyne vibration on stimulated Raman scattering (SRS) microscope to generate a quantitative three dimensional concentration map. Cancer cells with differing metabolic characteristics can be distinguished. Heterogeneous uptake patterns are observed in tumor xenograft tissues, neuronal culture and mouse brain tissues with clear cell-cell variations. Therefore, by offering the distinct advantage of optical resolution but without the undesirable influence of bulky fluorophores, our method of coupling SRS with alkyne labeled glucose will be an attractive tool to study energy demands of living systems at the single cell level.

Label-free biomolecular characterization of human breast cancer tissue with stimulated Raman scattering (SRS) spectral imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lu, Fa-Ke F.; Calligaris, David; Suo, Yuanzhen; Santagata, Sandro; Golby, Alexandra J.; Xie, X. Sunney; Mallory, Melissa A.; Golshan, Mehra; Dillon, Deborah A.; Agar, Nathalie Y. R.

2017-02-01

Stimulated Raman scattering (SRS) microscopy has been used for rapid label-free imaging of various biomolecules and drugs in living cells and tissues (Science, doi:10.1126/science.aaa8870). Our recent work has demonstrated that lipid and protein mapping of cancer tissue renders pathology-like images, providing essential histopathological information with subcellular resolution of the entire specimen (Cancer Research, doi: 10.1158/0008-5472.CAN-16-027). We have also established the first SRS imaging Atlas of human brain tumors (Harvard Dataverse, doi: (doi:10.7910/DVN/EZW4EK). SRS imaging of tissue could provide invaluable information for cancer diagnosis and surgical guidance in two aspects: rapid surgical pathology and quantitative biomolecular characterization. In this work, we present the use of SRS microscopy for characterization of a few essential biomolecules in breast cancer. Human breast cancer tissue specimens at the tumor core, tumor margin and normal area (5 cm away from the tumor) from surgical cases will be imaged with SRS at multiple Raman shifts, including the peaks for lipid, protein, blood (absorption), collagen, microcalcification (calcium phosphates and calcium oxalate) and carotenoids. Most of these Raman shifts have relatively strong Raman cross sections, which ensures high-quality and fast imaging. This proof-of-principle study is sought to demonstrate the feasibility and potential of SRS imaging for ambient diagnosis and surgical guidance of breast cancer.

Multiplexed aberration measurement for deep tissue imaging in vivo

PubMed Central

Wang, Chen; Liu, Rui; Milkie, Daniel E.; Sun, Wenzhi; Tan, Zhongchao; Kerlin, Aaron; Chen, Tsai-Wen; Kim, Douglas S.; Ji, Na

2014-01-01

We describe a multiplexed aberration measurement method that modulates the intensity or phase of light rays at multiple pupil segments in parallel to determine their phase gradients. Applicable to fluorescent-protein-labeled structures of arbitrary complexity, it allows us to obtain diffraction-limited resolution in various samples in vivo. For the strongly scattering mouse brain, a single aberration correction improves structural and functional imaging of fine neuronal processes over a large imaging volume. PMID:25128976

Spatial Frequency Domain Imaging: Applications in Preclinical Models of Alzheimer's Disease

NASA Astrophysics Data System (ADS)

Lin, Alexander Justin

A clinical challenge in Alzheimer's disease (AD) is diagnosing and treating patients earlier, before symptoms of cognitive dysfunction occur. A good screening test would be sensitive to the AD brain pathology, safe, and cost-effective. Diffuse optical imaging, which measures how non-ionizing light is absorbed and scattered in tissue, may fulfill these three parameters. We imaged the brains of transgenic AD mouse models in vivo with a quantitative, camera-based, diffuse optical imaging technology called spatial frequency domain imaging (SFDI) to characterize near-infrared (650-970nm) optical biomarkers of AD. Compared to age-matched control mice, we found a decrease in light absorption --- due to lower oxygenated and total hemoglobin concentrations in the brain --- correlating to decreased blood vessel volume and density in histology. Light scattering also increased in AD mice, correlating to brain structural changes caused by neuron loss and activation of inflammatory cells. Furthermore, inhaled gas challenges revealed brain vascular function was diminished. To investigate how AD affects the small changes in blood perfusion caused by increased brain activity, we built a new SFDI system from a commercial light-emitting diode microprojector and off-the-shelf optical components and cameras to measure optical properties in the visible range (460-632nm). Our measurements showed a reduced amplitude and duration of blood vessel dilation to increased brain activity in the AD mice. Altogether, this work increased our understanding of AD pathogenesis, explored optical biomarkers of AD, and improved technology access to other research labs. These results and technologies can further be used to facilitate longitudinal drug therapy trials in mice and provide a roadmap to diffuse optical spectroscopy studies in humans.

Plum pudding random medium model of biological tissue toward remote microscopy from spectroscopic light scattering

PubMed Central

Xu, Min

2017-01-01

Biological tissue has a complex structure and exhibits rich spectroscopic behavior. There has been no tissue model until now that has been able to account for the observed spectroscopy of tissue light scattering and its anisotropy. Here we present, for the first time, a plum pudding random medium (PPRM) model for biological tissue which succinctly describes tissue as a superposition of distinctive scattering structures (plum) embedded inside a fractal continuous medium of background refractive index fluctuation (pudding). PPRM faithfully reproduces the wavelength dependence of tissue light scattering and attributes the “anomalous” trend in the anisotropy to the plum and the powerlaw dependence of the reduced scattering coefficient to the fractal scattering pudding. Most importantly, PPRM opens up a novel venue of quantifying the tissue architecture and microscopic structures on average from macroscopic probing of the bulk with scattered light alone without tissue excision. We demonstrate this potential by visualizing the fine microscopic structural alterations in breast tissue (adipose, glandular, fibrocystic, fibroadenoma, and ductal carcinoma) deduced from noncontact spectroscopic measurement. PMID:28663913

Optical coherence tomography and optical coherence domain reflectometry for deep brain stimulation probe guidance

NASA Astrophysics Data System (ADS)

Jeon, Sung W.; Shure, Mark A.; Baker, Kenneth B.; Chahlavi, Ali; Hatoum, Nagi; Turbay, Massud; Rollins, Andrew M.; Rezai, Ali R.; Huang, David

2005-04-01

Deep Brain Stimulation (DBS) is FDA-approved for the treatment of Parkinson's disease and essential tremor. Currently, placement of DBS leads is guided through a combination of anatomical targeting and intraoperative microelectrode recordings. The physiological mapping process requires several hours, and each pass of the microelectrode into the brain increases the risk of hemorrhage. Optical Coherence Domain Reflectometry (OCDR) in combination with current methodologies could reduce surgical time and increase accuracy and safety by providing data on structures some distance ahead of the probe. For this preliminary study, we scanned a rat brain in vitro using polarization-insensitive Optical Coherence Tomography (OCT). For accurate measurement of intensity and attenuation, polarization effects arising from tissue birefringence are removed by polarization diversity detection. A fresh rat brain was sectioned along the coronal plane and immersed in a 5 mm cuvette with saline solution. OCT images from a 1294 nm light source showed depth profiles up to 2 mm. Light intensity and attenuation rate distinguished various tissue structures such as hippocampus, cortex, external capsule, internal capsule, and optic tract. Attenuation coefficient is determined by linear fitting of the single scattering regime in averaged A-scans where Beer"s law is applicable. Histology showed very good correlation with OCT images. From the preliminary study using OCT, we conclude that OCDR is a promising approach for guiding DBS probe placement.

Utilization of functional near infrared spectroscopy for non-invasive evaluation

NASA Astrophysics Data System (ADS)

Halim, A. A. A.; Laili, M. H.; Aziz, N. A.; Laili, A. R.; Salikin, M. S.; Rusop, M.

2016-07-01

The goal of this brief review is to report the techniques of functional near infrared spectroscopy for non-invasive evaluation in human study. The development of functional near infrared spectroscopy (fNIRS) technologies has advanced quantification signal using multiple wavelength and detector to solve the propagation of light inside the tissues including the absorption, scattering coefficient and to define the light penetration into tissues multilayers. There are a lot of studies that demonstrate signal from fNIRS which can be used to evaluate the changes of oxygenation level and measure the limitation of muscle performance in human brain and muscle tissues. Comprehensive reviews of diffuse reflectance based on beer lambert law theory were presented in this paper. The principle and development of fNIRS instrumentation is reported in detail.

Transcranial light-tissue interaction analysis

NASA Astrophysics Data System (ADS)

Aulakh, Kavleen; Zakaib, Scott; Willmore, William G.; Ye, Winnie N.

2016-03-01

The penetration depth of light plays a crucial role in therapeutic medical applications. In order to design effective medical photonic devices, an in-depth understanding of light's ability to penetrate tissues (including bone, skin, and fat) is necessary. The amount of light energy absorbed or scattered by tissues affects the intensity of light reaching an intended target in vivo. In this study, we examine the transmittance of light through a variety of cranial tissues for the purpose of determining the efficacy of neuro stimulation using a transcranial laser. Tissue samples collected from a pig were irradiated with a pulsed laser. We first determine the optimal irradiation wavelength of the laser to be 808nm. With varying peak and average power of the laser, we found an inverse and logarithmic relationship between the penetration depth and the intensity of the light. After penetrating the skin and skull of the pig, the light decreases in intensity at a rate of approximately 90.8 (+/-0.4) percent for every 5 mm of brain tissue penetrated. We also found the correlation between the irradiation time and dosage, using three different lasers (with peak power of 500, 1000, and 1500mW respectively). These data will help deduce what laser power is required to achieve a clinically-realistic model for a given irradiation time. This work is fundamental and the experimental data can be used to supplement existing and future research on the effects of laser light on brain tissue for the design of medical devices.

Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

PubMed

Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

1999-05-01

Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

A wireless handheld probe with spectrally constrained evolution strategies for diffuse optical imaging of tissue

NASA Astrophysics Data System (ADS)

Flexman, M. L.; Kim, H. K.; Stoll, R.; Khalil, M. A.; Fong, C. J.; Hielscher, A. H.

2012-03-01

We present a low-cost, portable, wireless diffuse optical imaging device. The handheld device is fast, portable, and can be applied to a wide range of both static and dynamic imaging applications including breast cancer, functional brain imaging, and peripheral artery disease. The continuous-wave probe has four near-infrared wavelengths and uses digital detection techniques to perform measurements at 2.3 Hz. Using a multispectral evolution algorithm for chromophore reconstruction, we can measure absolute oxygenated and deoxygenated hemoglobin concentration as well as scattering in tissue. Performance of the device is demonstrated using a series of liquid phantoms comprised of Intralipid®, ink, and dye.

Volumetric soft tissue brain imaging on xCAT, a mobile flat-panel x-ray CT system

NASA Astrophysics Data System (ADS)

Zbijewski, Wojciech; Stayman, J. Webster

2009-02-01

We discuss the ongoing development of soft-tissue imaging capabilities on xCAT, a highly portable, flat-panel based cone-beam X-ray CT platform. By providing the ability to rapidly detect intra-cranial bleeds and other symptoms of stroke directly at the patient's bedside, our new system can potentially significantly improve the management of neurological emergency and intensive care patients. The paper reports on the design of our system, as well as on the methods used to combat artifacts due to scatter, non-linear detector response and scintillator glare. Images of cadaveric head samples are also presented and compared with conventional CT scans.

Neuroscience imaging enabled by new highly tunable and high peak power femtosecond lasers

NASA Astrophysics Data System (ADS)

Hakulinen, T.; Klein, J.

2017-02-01

Neuroscience applications benefit from recent developments in industrial femtosecond laser technology. New laser sources provide several megawatts of peak power at wavelength of 1040 nm, which enables simultaneous optogenetics photoactivation of tens or even hundreds of neurons using red shifted opsins. Another recent imaging trend is to move towards longer wavelengths, which would enable access to deeper layers of tissue due to lower scattering and lower absorption in the tissue. Femtosecond lasers pumping a non-collinear optical parametric amplifier (NOPA) enable the access to longer wavelengths with high peak powers. High peak powers of >10 MW at 1300 nm and 1700 nm allow effective 3-photon excitation of green and red shifted calcium indicators respectively and access to deeper, sub-cortex layers of the brain. Early results include in vivo detection of spontaneous activity in hippocampus within an intact mouse brain, where neurons express GCaMP6 activated in a 3-photon process at 1320 nm.

SU-E-I-44: Some Preliminary Analysis of Angular Distribution of X-Ray Scattered On Soft Tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganezer, K; Krmar, M; Cvejic, Z

2015-06-15

Purpose: The angular distribution of x-radiation scattered at small angles (up to 16 degrees) from several different animal soft tissue (skin, fat, muscle, retina, etc) were measured using standard equipment devoted to study of crystal structure which provides excellent geometry conditions of measurements. showed measurable differences for different tissues. In the simplest possible case when measured samples do not differ in structure (different concentration solutions) it can be seen that intensity of scattered radiation is decreasing function of the concentration and the peak of the maximum of scattering distribution depends on the concentration as well. Methods: An x-ray scattering profilemore » usually consists of sharp diffraction peak; however some properties of the spatial profiles of scattered radiation as intensity, the peak position, height, area, FWHM, the ratio of peak heights, etc. Results: The data contained measurable differences for different tissues. In the simplest possible case when measured samples do not differ in structure (different concentration solutions) it can be seen that intensity of scattered radiation is decreasing function of the concentration and the peak of the maximum of scattering distribution depends on the concentration as well. Measurements of different samples in the very preliminary phase showed that simple biological material used in study showed slightly different scattering pattern, especially at higher angles (around 10degrees). Intensity of radiation scattered from same tissue type is very dependent on water content and several more parameters. Conclusion: This preliminary study using animal soft tissues on the angular distributions of scattered x-rays suggests that angular distributions of X-rays scattered off of soft tissues might be useful in distinguishing healthy tissue from malignant soft tissue.« less

Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain

PubMed Central

Tian, Peifang; Devor, Anna; Sakadžić, Sava; Dale, Anders M.; Boas, David A.

2011-01-01

Absorption or fluorescence-based two-dimensional (2-D) optical imaging is widely employed in functional brain imaging. The image is a weighted sum of the real signal from the tissue at different depths. This weighting function is defined as “depth sensitivity.” Characterizing depth sensitivity and spatial resolution is important to better interpret the functional imaging data. However, due to light scattering and absorption in biological tissues, our knowledge of these is incomplete. We use Monte Carlo simulations to carry out a systematic study of spatial resolution and depth sensitivity for 2-D optical imaging methods with configurations typically encountered in functional brain imaging. We found the following: (i) the spatial resolution is <200 μm for NA ≤0.2 or focal plane depth ≤300 μm. (ii) More than 97% of the signal comes from the top 500 μm of the tissue. (iii) For activated columns with lateral size larger than spatial resolution, changing numerical aperature (NA) and focal plane depth does not affect depth sensitivity. (iv) For either smaller columns or large columns covered by surface vessels, increasing NA and∕or focal plane depth may improve depth sensitivity at deeper layers. Our results provide valuable guidance for the optimization of optical imaging systems and data interpretation. PMID:21280912

Microscopic Imaging and Spectroscopy with Scattered Light

PubMed Central

Boustany, Nada N.; Boppart, Stephen A.; Backman, Vadim

2012-01-01

Optical contrast based on elastic scattering interactions between light and matter can be used to probe cellular structure and dynamics, and image tissue architecture. The quantitative nature and high sensitivity of light scattering signals to subtle alterations in tissue morphology, as well as the ability to visualize unstained tissue in vivo, has recently generated significant interest in optical scatter based biosensing and imaging. Here we review the fundamental methodologies used to acquire and interpret optical scatter data. We report on recent findings in this field and present current advances in optical scatter techniques and computational methods. Cellular and tissue data enabled by current advances in optical scatter spectroscopy and imaging stand to impact a variety of biomedical applications including clinical tissue diagnosis, in vivo imaging, drug discovery and basic cell biology. PMID:20617940

Biophysical interpretation and ex-vivo characterization of scattered light from tumor-associated breast stroma

NASA Astrophysics Data System (ADS)

Laughney, Ashley; Krishnaswamy, Venkat; Schwab, Mary; Wells, Wendy A.; Paulsen, Keith D.; Pogue, Brian W.

2009-02-01

The purpose of this study was to extract scatter parameters related to tissue ultra-structures from freshly excised breast tissue and to assess whether evident changes in scatter across diagnostic categories is primarily influenced by variation in the composition of each tissues subtypes or by physical remodeling of the extra-cellular environment. Pathologists easily distinguish between epithelium, stroma and adipose tissues, so this classification was adopted for macroscopic subtype classification. Micro-sampling reflectance spectroscopy was used to characterize single-backscattered photons from fresh, excised tumors and normal reduction specimens with sub-millimeter resolution. Phase contrast microscopy (sub-micron resolution) was used to characterize forward-scattered light through frozen tissue from the DHMC Tissue Bank, representing normal, benign and malignant breast tissue, sectioned at 10 microns. The packing density and orientation of collagen fibers in the extracellular matrix (ECM) associated with invasive, normal and benign epithelium was evaluated using transmission electron microscopy (TEM). Regions of interest (ROIs) in the H&E stained tissues were identified for analysis, as outlined by a pathologist as the gold standard. We conclude that the scatter parameters associated with tumor specimens (Npatients=6, Nspecimens=13) significantly differs from that of normal reductions (Npatients=6, Nspecimens=10). Further, tissue subtypes may be identified by their scatter spectra at sub-micron resolution. Stromal tissue scatters significantly more than the epithelial cells embedded in its ECM and adipose tissue scatters much less. However, the scatter signature of the stroma at the sub-micron level is not particularly differentiating in terms of a diagnosis.

Two-photon microscope for multisite microphotolysis of caged neurotransmitters in acute brain slices

PubMed Central

Losavio, Bradley E.; Iyer, Vijay; Saggau, Peter

2009-01-01

We developed a two-photon microscope optimized for physiologically manipulating single neurons through their postsynaptic receptors. The optical layout fulfills the stringent design criteria required for high-speed, high-resolution imaging in scattering brain tissue with minimal photodamage. We detail the practical compensation of spectral and temporal dispersion inherent in fast laser beam scanning with acousto-optic deflectors, as well as a set of biological protocols for visualizing nearly diffraction-limited structures and delivering physiological synaptic stimuli. The microscope clearly resolves dendritic spines and evokes electrophysiological transients in single neurons that are similar to endogenous responses. This system enables the study of multisynaptic integration and will assist our understanding of single neuron function and dendritic computation. PMID:20059271

Dual-modality optical biopsy of glioblastomas multiforme with diffuse reflectance and fluorescence: ex vivo retrieval of optical properties

NASA Astrophysics Data System (ADS)

Du Le, Vinh Nguyen; Provias, John; Murty, Naresh; Patterson, Michael S.; Nie, Zhaojun; Hayward, Joseph E.; Farrell, Thomas J.; McMillan, William; Zhang, Wenbin; Fang, Qiyin

2017-02-01

Glioma itself accounts for 80% of all malignant primary brain tumors, and glioblastoma multiforme (GBM) accounts for 55% of such tumors. Diffuse reflectance and fluorescence spectroscopy have the potential to discriminate healthy tissues from abnormal tissues and therefore are promising noninvasive methods for improving the accuracy of brain tissue resection. Optical properties were retrieved using an experimentally evaluated inverse solution. On average, the scattering coefficient is 2.4 times higher in GBM than in low grade glioma (LGG), and the absorption coefficient is 48% higher. In addition, the ratio of fluorescence to diffuse reflectance at the emission peak of 460 nm is 2.6 times higher for LGG while reflectance at 650 nm is 2.7 times higher for GBM. The results reported also show that the combination of diffuse reflectance and fluorescence spectroscopy could achieve sensitivity of 100% and specificity of 90% in discriminating GBM from LGG during ex vivo measurements of 22 sites from seven glioma specimens. Therefore, the current technique might be a promising tool for aiding neurosurgeons in determining the extent of surgical resection of glioma and, thus, improving intraoperative tumor identification for guiding surgical intervention.

Dual-modality optical biopsy of glioblastomas multiforme with diffuse reflectance and fluorescence: ex vivo retrieval of optical properties.

PubMed

Du Le, Vinh Nguyen; Provias, John; Murty, Naresh; Patterson, Michael S; Nie, Zhaojun; Hayward, Joseph E; Farrell, Thomas J; McMillan, William; Zhang, Wenbin; Fang, Qiyin

2017-02-01

Glioma itself accounts for 80% of all malignant primary brain tumors, and glioblastoma multiforme (GBM) accounts for 55% of such tumors. Diffuse reflectance and fluorescence spectroscopy have the potential to discriminate healthy tissues from abnormal tissues and therefore are promising noninvasive methods for improving the accuracy of brain tissue resection. Optical properties were retrieved using an experimentally evaluated inverse solution. On average, the scattering coefficient is 2.4 times higher in GBM than in low grade glioma (LGG), and the absorption coefficient is 48% higher. In addition, the ratio of fluorescence to diffuse reflectance at the emission peak of 460 nm is 2.6 times higher for LGG while reflectance at 650 nm is 2.7 times higher for GBM. The results reported also show that the combination of diffuse reflectance and fluorescence spectroscopy could achieve sensitivity of 100% and specificity of 90% in discriminating GBM from LGG during ex vivo measurements of 22 sites from seven glioma specimens. Therefore, the current technique might be a promising tool for aiding neurosurgeons in determining the extent of surgical resection of glioma and, thus, improving intraoperative tumor identification for guiding surgical intervention.

Quantitative Imaging of Scattering Changes Associated With Epithelial Proliferation, Necrosis and Fibrosis in Tumors Using Microsampling Reflectance Spectroscopy

PubMed Central

Krishnaswamy, Venkataramanan; Hoopes, P. Jack; Samkoe, Kimberley S.; O'Hara, Julia A.; Hasan, Tayyaba; Pogue, Brian W.

2010-01-01

Highly localized reflectance measurements can be used to directly quantify scatter changes in tissues. This study presents a microsampling approach that is used to raster scan tumors to extract parameters believed to be related to the tissue ultra-structure. A confocal reflectance imager was developed to examine scatter changes across pathologically distinct regions within tumor tissues. Tissue sections from two murine tumors, AsPC-1 pancreas tumor and the Mat-LyLu Dunning prostate tumor, were imaged. After imaging, histopathology-guided region-of-interest studies of the images allowed analysis of the variations in scattering resulting from differences in tissue ultra-structure. On average, the median scatter power of tumor cells with high proliferation index was about 26% less compared to tumor cells with low proliferation index (LPI). Necrosis exhibited the lowest scatter power signature across all the tissue types considered, with about 55% lower median scatter power than LPI tumor cells. Additionally, the level and maturity of the tumor's fibroplastic response was found to influence the scatter signal. This approach to scatter visualization of tissue ultra-structure in situ could provide a unique tool for guiding surgical resection, but this kind of interpretation into what the signal means relative to the pathology is required before proceeding to clinical studies. PMID:19256692

Three-dimensional fuse deposition modeling of tissue-simulating phantom for biomedical optical imaging

NASA Astrophysics Data System (ADS)

Dong, Erbao; Zhao, Zuhua; Wang, Minjie; Xie, Yanjun; Li, Shidi; Shao, Pengfei; Cheng, Liuquan; Xu, Ronald X.

2015-12-01

Biomedical optical devices are widely used for clinical detection of various tissue anomalies. However, optical measurements have limited accuracy and traceability, partially owing to the lack of effective calibration methods that simulate the actual tissue conditions. To facilitate standardized calibration and performance evaluation of medical optical devices, we develop a three-dimensional fuse deposition modeling (FDM) technique for freeform fabrication of tissue-simulating phantoms. The FDM system uses transparent gel wax as the base material, titanium dioxide (TiO2) powder as the scattering ingredient, and graphite powder as the absorption ingredient. The ingredients are preheated, mixed, and deposited at the designated ratios layer-by-layer to simulate tissue structural and optical heterogeneities. By printing the sections of human brain model based on magnetic resonance images, we demonstrate the capability for simulating tissue structural heterogeneities. By measuring optical properties of multilayered phantoms and comparing with numerical simulation, we demonstrate the feasibility for simulating tissue optical properties. By creating a rat head phantom with embedded vasculature, we demonstrate the potential for mimicking physiologic processes of a living system.

TH-AB-209-10: Breast Cancer Identification Through X-Ray Coherent Scatter Spectral Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kapadia, A; Morris, R; Albanese, K

Purpose: We have previously described the development and testing of a coherent-scatter spectral imaging system for identification of cancer. Our prior evaluations were performed using either tissue surrogate phantoms or formalin-fixed tissue obtained from pathology. Here we present the first results from a scatter imaging study using fresh breast tumor tissues obtained through surgical excision. Methods: A coherent-scatter imaging system was built using a clinical X-ray tube, photon counting detectors, and custom-designed coded-apertures. System performance was characterized using calibration phantoms of biological materials. Fresh breast tumors were obtained from patients undergoing mastectomy and lumpectomy surgeries for breast cancer. Each specimenmore » was vacuum-sealed, scanned using the scatter imaging system, and then sent to pathology for histological workup. Scatter images were generated separately for each tissue specimen and analyzed to identify voxels containing malignant tissue. The images were compared against histological analysis (H&E + pathologist identification of tumors) to assess the match between scatter-based and histological diagnosis. Results: In all specimens scanned, the scatter images showed the location of cancerous regions within the specimen. The detection and classification was performed through automated spectral matching without the need for manual intervention. The scatter spectra corresponding to cancer tissue were found to be in agreement with those reported in literature. Inter-patient variability was found to be within limits reported in literature. The scatter images showed agreement with pathologist-identified regions of cancer. Spatial resolution for this configuration of the scanner was determined to be 2–3 mm, and the total scan time for each specimen was under 15 minutes. Conclusion: This work demonstrates the utility of coherent scatter imaging in identifying cancer based on the scatter properties of the tissue. It presents the first results from coherent scatter imaging of fresh (unfixed) breast tissue using our coded-aperture scatter imaging approach for cancer identification.« less

Parallel Solver for Diffuse Optical Tomography on Realistic Head Models With Scattering and Clear Regions.

PubMed

Placati, Silvio; Guermandi, Marco; Samore, Andrea; Scarselli, Eleonora Franchi; Guerrieri, Roberto

2016-09-01

Diffuse optical tomography is an imaging technique, based on evaluation of how light propagates within the human head to obtain the functional information about the brain. Precision in reconstructing such an optical properties map is highly affected by the accuracy of the light propagation model implemented, which needs to take into account the presence of clear and scattering tissues. We present a numerical solver based on the radiosity-diffusion model, integrating the anatomical information provided by a structural MRI. The solver is designed to run on parallel heterogeneous platforms based on multiple GPUs and CPUs. We demonstrate how the solver provides a 7 times speed-up over an isotropic-scattered parallel Monte Carlo engine based on a radiative transport equation for a domain composed of 2 million voxels, along with a significant improvement in accuracy. The speed-up greatly increases for larger domains, allowing us to compute the light distribution of a full human head ( ≈ 3 million voxels) in 116 s for the platform used.

Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

PubMed Central

Srinivasan, Vivek J.; Mandeville, Emiri T.; Can, Anil; Blasi, Francesco; Climov, Mihail; Daneshmand, Ali; Lee, Jeong Hyun; Yu, Esther; Radhakrishnan, Harsha; Lo, Eng H.; Sakadžić, Sava; Eikermann-Haerter, Katharina; Ayata, Cenk

2013-01-01

Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties. PMID:23940761

Effects of formalin fixation on tissue optical properties of in-vitro brain samples

NASA Astrophysics Data System (ADS)

Anand, Suresh; Cicchi, Riccardo; Martelli, Fabrizio; Giordano, Flavio; Buccoliero, Anna Maria; Guerrini, Renzo; Pavone, Francesco S.

2015-03-01

Application of light spectroscopy based techniques for the detection of cancers have emerged as a promising approach for tumor diagnostics. In-vivo or freshly excised samples are normally used for point spectroscopic studies. However, ethical issues related to in-vivo studies, rapid decay of surgically excised tissues and sample availability puts a limitation on in-vivo and in-vitro studies. There has been a few studies reported on the application of formalin fixed samples with good discrimination capability. Usually formalin fixation is performed to prevent degradation of tissues after surgical resection. Fixing tissues in formalin prevents cell death by forming cross-linkages with proteins. Previous investigations have revealed that washing tissues fixed in formalin using phosphate buffered saline is known to reduce the effects of formalin during spectroscopic measurements. But this could not be the case with reflectance measurements. Hemoglobin is a principal absorbing medium in biological tissues in the visible range. Formalin fixation causes hemoglobin to seep out from red blood cells. Also, there could be alterations in the refractive index of tissues when fixed in formalin. In this study, we propose to investigate the changes in tissue optical properties between freshly excised and formalin fixed brain tissues. The results indicate a complete change in the spectral profile in the visible range where hemoglobin has its maximum absorption peaks. The characteristic bands of oxy-hemoglobin at 540, 580 nm and deoxy-hemoglobin at 555 nm disappear in the case of samples fixed in formalin. In addition, an increased spectral intensity was observed for the wavelengths greater than 650 nm where scattering phenomena are presumed to dominate.

Influence of multiple scattering and absorption on the full scattering profile and the isobaric point in tissue

NASA Astrophysics Data System (ADS)

Duadi, Hamootal; Fixler, Dror

2015-05-01

Light reflectance and transmission from soft tissue has been utilized in noninvasive clinical measurement devices such as the photoplethysmograph (PPG) and reflectance pulse oximeter. Incident light on the skin travels into the underlying layers and is in part reflected back to the surface, in part transferred and in part absorbed. Most methods of near infrared (NIR) spectroscopy focus on the volume reflectance from a semi-infinite sample, while very few measure transmission. We have previously shown that examining the full scattering profile (angular distribution of exiting photons) provides more comprehensive information when measuring from a cylindrical tissue. Furthermore, an isobaric point was found which is not dependent on changes in the reduced scattering coefficient. The angle corresponding to this isobaric point depends on the tissue diameter. We investigated the role of multiple scattering and absorption on the full scattering profile of a cylindrical tissue. First, we define the range in which multiple scattering occurs for different tissue diameters. Next, we examine the role of the absorption coefficient in the attenuation of the full scattering profile. We demonstrate that the absorption linearly influences the intensity at each angle of the full scattering profile and, more importantly, the absorption does not change the position of the isobaric point. The findings of this work demonstrate a realistic model for optical tissue measurements such as NIR spectroscopy, PPG, and pulse oximetery.

Deep Tissue Fluorescent Imaging in Scattering Specimens Using Confocal Microscopy

PubMed Central

Clendenon, Sherry G.; Young, Pamela A.; Ferkowicz, Michael; Phillips, Carrie; Dunn, Kenneth W.

2015-01-01

In scattering specimens, multiphoton excitation and nondescanned detection improve imaging depth by a factor of 2 or more over confocal microscopy; however, imaging depth is still limited by scattering. We applied the concept of clearing to deep tissue imaging of highly scattering specimens. Clearing is a remarkably effective approach to improving image quality at depth using either confocal or multiphoton microscopy. Tissue clearing appears to eliminate the need for multiphoton excitation for deep tissue imaging. PMID:21729357

Evaluation of light scattering properties and chromophore concentrations in skin tissue based on diffuse reflectance signals at isosbestic wavelengths of hemoglobin

NASA Astrophysics Data System (ADS)

Yokokawa, Takumi; Nishidate, Izumi

2016-04-01

We investigate a method to evaluate light-scattering properties and chromophore concentrations in human skin tissue through diffuse reflectance spectroscopy using the reflectance signals acquired at isosbestic wavelengths of hemoglobin (420, 450, 500, and 585 nm). In the proposed method, Monte Carlo simulation-based empirical formulas are used to specify the scattering parameters of skin tissue, such as the scattering amplitude a and the scattering power b, as well as the concentration of melanin C m and the total blood concentration C tb. The use of isosbestic wavelengths of hemoglobin enables the values of C m, C tb, a, and b to be estimated independently of the oxygenation of hemoglobin. The spectrum of the reduced scattering coefficient is reconstructed from the scattering parameters. Experiments using in vivo human skin tissues were performed to confirm the feasibility of the proposed method for evaluating the changes in scattering properties and chromophore concentrations in skin tissue. The experimental results revealed that light scattering is significantly reduced by the application of a glycerol solution, which indicates an optical clearing effect due to osmotic dehydration and the matching of the refractive indices of scatterers in the epidermis.

Tissue mimicking simulations for temporal enhanced ultrasound-based tissue typing

NASA Astrophysics Data System (ADS)

Bayat, Sharareh; Imani, Farhad; Gerardo, Carlos D.; Nir, Guy; Azizi, Shekoofeh; Yan, Pingkun; Tahmasebi, Amir; Wilson, Storey; Iczkowski, Kenneth A.; Lucia, M. Scott; Goldenberg, Larry; Salcudean, Septimiu E.; Mousavi, Parvin; Abolmaesumi, Purang

2017-03-01

Temporal enhanced ultrasound (TeUS) is an imaging approach where a sequence of temporal ultrasound data is acquired and analyzed for tissue typing. Previously, in a series of in vivo and ex vivo studies we have demonstrated that, this approach is effective for detecting prostate and breast cancers. Evidences derived from our experiments suggest that both ultrasound-signal related factors such as induced heat and tissue-related factors such as the distribution and micro-vibration of scatterers lead to tissue typing information in TeUS. In this work, we simulate mechanical micro-vibrations of scatterers in tissue-mimicking phantoms that have various scatterer densities reflecting benign and cancerous tissue structures. Finite element modeling (FEM) is used for this purpose where the vertexes are scatterers representing cell nuclei. The initial positions of scatterers are determined by the distribution of nuclei segmented from actual digital histology scans of prostate cancer patients. Subsequently, we generate ultrasound images of the simulated tissue structure using the Field II package resulting in a temporal enhanced ultrasound. We demonstrate that the micro-vibrations of scatterers are captured by temporal ultrasound data and this information can be exploited for tissue typing.

Tissue Equivalent Phantom Design for Characterization of a Coherent Scatter X-ray Imaging System

NASA Astrophysics Data System (ADS)

Albanese, Kathryn Elizabeth

Scatter in medical imaging is typically cast off as image-related noise that detracts from meaningful diagnosis. It is therefore typically rejected or removed from medical images. However, it has been found that every material, including cancerous tissue, has a unique X-ray coherent scatter signature that can be used to identify the material or tissue. Such scatter-based tissue-identification provides the advantage of locating and identifying particular materials over conventional anatomical imaging through X-ray radiography. A coded aperture X-ray coherent scatter spectral imaging system has been developed in our group to classify different tissue types based on their unique scatter signatures. Previous experiments using our prototype have demonstrated that the depth-resolved coherent scatter spectral imaging system (CACSSI) can discriminate healthy and cancerous tissue present in the path of a non-destructive x-ray beam. A key to the successful optimization of CACSSI as a clinical imaging method is to obtain anatomically accurate phantoms of the human body. This thesis describes the development and fabrication of 3D printed anatomical scatter phantoms of the breast and lung. The purpose of this work is to accurately model different breast geometries using a tissue equivalent phantom, and to classify these tissues in a coherent x-ray scatter imaging system. Tissue-equivalent anatomical phantoms were designed to assess the capability of the CACSSI system to classify different types of breast tissue (adipose, fibroglandular, malignant). These phantoms were 3D printed based on DICOM data obtained from CT scans of prone breasts. The phantoms were tested through comparison of measured scatter signatures with those of adipose and fibroglandular tissue from literature. Tumors in the phantom were modeled using a variety of biological tissue including actual surgically excised benign and malignant tissue specimens. Lung based phantoms have also been printed for future testing. Our imaging system has been able to define the location and composition of the various materials in the phantom. These phantoms were used to characterize the CACSSI system in terms of beam width and imaging technique. The result of this work showed accurate modeling and characterization of the phantoms through comparison of the tissue-equivalent form factors to those from literature. The physical construction of the phantoms, based on actual patient anatomy, was validated using mammography and computed tomography to visually compare the clinical images to those of actual patient anatomy.

Inverse scattering approach to improving pattern recognition

NASA Astrophysics Data System (ADS)

Chapline, George; Fu, Chi-Yung

2005-05-01

The Helmholtz machine provides what may be the best existing model for how the mammalian brain recognizes patterns. Based on the observation that the "wake-sleep" algorithm for training a Helmholtz machine is similar to the problem of finding the potential for a multi-channel Schrodinger equation, we propose that the construction of a Schrodinger potential using inverse scattering methods can serve as a model for how the mammalian brain learns to extract essential information from sensory data. In particular, inverse scattering theory provides a conceptual framework for imagining how one might use EEG and MEG observations of brain-waves together with sensory feedback to improve human learning and pattern recognition. Longer term, implementation of inverse scattering algorithms on a digital or optical computer could be a step towards mimicking the seamless information fusion of the mammalian brain.

Inverse Scattering Approach to Improving Pattern Recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapline, G; Fu, C

2005-02-15

The Helmholtz machine provides what may be the best existing model for how the mammalian brain recognizes patterns. Based on the observation that the ''wake-sleep'' algorithm for training a Helmholtz machine is similar to the problem of finding the potential for a multi-channel Schrodinger equation, we propose that the construction of a Schrodinger potential using inverse scattering methods can serve as a model for how the mammalian brain learns to extract essential information from sensory data. In particular, inverse scattering theory provides a conceptual framework for imagining how one might use EEG and MEG observations of brain-waves together with sensorymore » feedback to improve human learning and pattern recognition. Longer term, implementation of inverse scattering algorithms on a digital or optical computer could be a step towards mimicking the seamless information fusion of the mammalian brain.« less

Development of a practical image-based scatter correction method for brain perfusion SPECT: comparison with the TEW method.

PubMed

Shidahara, Miho; Watabe, Hiroshi; Kim, Kyeong Min; Kato, Takashi; Kawatsu, Shoji; Kato, Rikio; Yoshimura, Kumiko; Iida, Hidehiro; Ito, Kengo

2005-10-01

An image-based scatter correction (IBSC) method was developed to convert scatter-uncorrected into scatter-corrected SPECT images. The purpose of this study was to validate this method by means of phantom simulations and human studies with 99mTc-labeled tracers, based on comparison with the conventional triple energy window (TEW) method. The IBSC method corrects scatter on the reconstructed image I(mub)AC with Chang's attenuation correction factor. The scatter component image is estimated by convolving I(mub)AC with a scatter function followed by multiplication with an image-based scatter fraction function. The IBSC method was evaluated with Monte Carlo simulations and 99mTc-ethyl cysteinate dimer SPECT human brain perfusion studies obtained from five volunteers. The image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were compared. Using data obtained from the simulations, the image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were found to be nearly identical for both gray and white matter. In human brain images, no significant differences in image contrast were observed between the IBSC and TEW methods. The IBSC method is a simple scatter correction technique feasible for use in clinical routine.

Design and implementation of coded aperture coherent scatter spectral imaging of cancerous and healthy breast tissue samples

PubMed Central

Lakshmanan, Manu N.; Greenberg, Joel A.; Samei, Ehsan; Kapadia, Anuj J.

2016-01-01

Abstract. A scatter imaging technique for the differentiation of cancerous and healthy breast tissue in a heterogeneous sample is introduced in this work. Such a technique has potential utility in intraoperative margin assessment during lumpectomy procedures. In this work, we investigate the feasibility of the imaging method for tumor classification using Monte Carlo simulations and physical experiments. The coded aperture coherent scatter spectral imaging technique was used to reconstruct three-dimensional (3-D) images of breast tissue samples acquired through a single-position snapshot acquisition, without rotation as is required in coherent scatter computed tomography. We perform a quantitative assessment of the accuracy of the cancerous voxel classification using Monte Carlo simulations of the imaging system; describe our experimental implementation of coded aperture scatter imaging; show the reconstructed images of the breast tissue samples; and present segmentations of the 3-D images in order to identify the cancerous and healthy tissue in the samples. From the Monte Carlo simulations, we find that coded aperture scatter imaging is able to reconstruct images of the samples and identify the distribution of cancerous and healthy tissues (i.e., fibroglandular, adipose, or a mix of the two) inside them with a cancerous voxel identification sensitivity, specificity, and accuracy of 92.4%, 91.9%, and 92.0%, respectively. From the experimental results, we find that the technique is able to identify cancerous and healthy tissue samples and reconstruct differential coherent scatter cross sections that are highly correlated with those measured by other groups using x-ray diffraction. Coded aperture scatter imaging has the potential to provide scatter images that automatically differentiate cancerous and healthy tissue inside samples within a time on the order of a minute per slice. PMID:26962543

Design and implementation of coded aperture coherent scatter spectral imaging of cancerous and healthy breast tissue samples.

PubMed

Lakshmanan, Manu N; Greenberg, Joel A; Samei, Ehsan; Kapadia, Anuj J

2016-01-01

A scatter imaging technique for the differentiation of cancerous and healthy breast tissue in a heterogeneous sample is introduced in this work. Such a technique has potential utility in intraoperative margin assessment during lumpectomy procedures. In this work, we investigate the feasibility of the imaging method for tumor classification using Monte Carlo simulations and physical experiments. The coded aperture coherent scatter spectral imaging technique was used to reconstruct three-dimensional (3-D) images of breast tissue samples acquired through a single-position snapshot acquisition, without rotation as is required in coherent scatter computed tomography. We perform a quantitative assessment of the accuracy of the cancerous voxel classification using Monte Carlo simulations of the imaging system; describe our experimental implementation of coded aperture scatter imaging; show the reconstructed images of the breast tissue samples; and present segmentations of the 3-D images in order to identify the cancerous and healthy tissue in the samples. From the Monte Carlo simulations, we find that coded aperture scatter imaging is able to reconstruct images of the samples and identify the distribution of cancerous and healthy tissues (i.e., fibroglandular, adipose, or a mix of the two) inside them with a cancerous voxel identification sensitivity, specificity, and accuracy of 92.4%, 91.9%, and 92.0%, respectively. From the experimental results, we find that the technique is able to identify cancerous and healthy tissue samples and reconstruct differential coherent scatter cross sections that are highly correlated with those measured by other groups using x-ray diffraction. Coded aperture scatter imaging has the potential to provide scatter images that automatically differentiate cancerous and healthy tissue inside samples within a time on the order of a minute per slice.

Optical scattering coefficient estimated by optical coherence tomography correlates with collagen content in ovarian tissue

NASA Astrophysics Data System (ADS)

Yang, Yi; Wang, Tianheng; Biswal, Nrusingh C.; Wang, Xiaohong; Sanders, Melinda; Brewer, Molly; Zhu, Quing

2011-09-01

Optical scattering coefficient from ex vivo unfixed normal and malignant ovarian tissue was quantitatively extracted by fitting optical coherence tomography (OCT) A-line signals to a single scattering model. 1097 average A-line measurements at a wavelength of 1310 nm were performed at 108 sites obtained from 18 ovaries. The average scattering coefficient obtained from the normal tissue group consisted of 833 measurements from 88 sites was 2.41 mm-1 (+/-0.59), while the average coefficient obtained from the malignant tissue group consisted of 264 measurements from 20 sites was 1.55 mm-1 (+/-0.46). The malignant ovarian tissue showed significant lower scattering than the normal group (p < 0.001). The amount of collagen within OCT imaging depth was analyzed from the tissue histological section stained with Sirius Red. The average collagen area fraction (CAF) obtained from the normal tissue group was 48.4% (+/-12.3%), while the average CAF obtained from the malignant tissue group was 11.4% (+/-4.7%). A statistical significance of the collagen content was found between the two groups (p < 0.001). These results demonstrated that quantitative measurements of optical scattering coefficient from OCT images could be a potential powerful method for ovarian cancer detection.

Label-free, multi-scale imaging of ex-vivo mouse brain using spatial light interference microscopy

NASA Astrophysics Data System (ADS)

Min, Eunjung; Kandel, Mikhail E.; Ko, Chemyong J.; Popescu, Gabriel; Jung, Woonggyu; Best-Popescu, Catherine

2016-12-01

Brain connectivity spans over broad spatial scales, from nanometers to centimeters. In order to understand the brain at multi-scale, the neural network in wide-field has been visualized in detail by taking advantage of light microscopy. However, the process of staining or addition of fluorescent tags is commonly required, and the image contrast is insufficient for delineation of cytoarchitecture. To overcome this barrier, we use spatial light interference microscopy to investigate brain structure with high-resolution, sub-nanometer pathlength sensitivity without the use of exogenous contrast agents. Combining wide-field imaging and a mosaic algorithm developed in-house, we show the detailed architecture of cells and myelin, within coronal olfactory bulb and cortical sections, and from sagittal sections of the hippocampus and cerebellum. Our technique is well suited to identify laminar characteristics of fiber tract orientation within white matter, e.g. the corpus callosum. To further improve the macro-scale contrast of anatomical structures, and to better differentiate axons and dendrites from cell bodies, we mapped the tissue in terms of its scattering property. Based on our results, we anticipate that spatial light interference microscopy can potentially provide multiscale and multicontrast perspectives of gross and microscopic brain anatomy.

Two-Photon Holographic Stimulation of ReaChR

PubMed Central

Chaigneau, Emmanuelle; Ronzitti, Emiliano; Gajowa, Marta A.; Soler-Llavina, Gilberto J.; Tanese, Dimitrii; Brureau, Anthony Y. B.; Papagiakoumou, Eirini; Zeng, Hongkui; Emiliani, Valentina

2016-01-01

Optogenetics provides a unique approach to remotely manipulate brain activity with light. Reaching the degree of spatiotemporal control necessary to dissect the role of individual cells in neuronal networks, some of which reside deep in the brain, requires joint progress in opsin engineering and light sculpting methods. Here we investigate for the first time two-photon stimulation of the red-shifted opsin ReaChR. We use two-photon (2P) holographic illumination to control the activation of individually chosen neurons expressing ReaChR in acute brain slices. We demonstrated reliable action potential generation in ReaChR-expressing neurons and studied holographic 2P-evoked spiking performances depending on illumination power and pulse width using an amplified laser and a standard femtosecond Ti:Sapphire oscillator laser. These findings provide detailed knowledge of ReaChR's behavior under 2P illumination paving the way for achieving in depth remote control of multiple cells with high spatiotemporal resolution deep within scattering tissue. PMID:27803649

Two-photon imaging in living brain slices.

PubMed

Mainen, Z F; Maletic-Savatic, M; Shi, S H; Hayashi, Y; Malinow, R; Svoboda, K

1999-06-01

Two-photon excitation laser scanning microscopy (TPLSM) has become the tool of choice for high-resolution fluorescence imaging in intact neural tissues. Compared with other optical techniques, TPLSM allows high-resolution imaging and efficient detection of fluorescence signal with minimal photobleaching and phototoxicity. The advantages of TPLSM are especially pronounced in highly scattering environments such as the brain slice. Here we describe our approaches to imaging various aspects of synaptic function in living brain slices. To combine several imaging modes together with patch-clamp electrophysiological recordings we found it advantageous to custom-build an upright microscope. Our design goals were primarily experimental convenience and efficient collection of fluorescence. We describe our TPLSM imaging system and its performance in detail. We present dynamic measurements of neuronal morphology of neurons expressing green fluorescent protein (GFP) and GFP fusion proteins as well as functional imaging of calcium dynamics in individual dendritic spines. Although our microscope is a custom instrument, its key advantages can be easily implemented as a modification of commercial laser scanning microscopes. Copyright 1999 Academic Press.

SU-E-T-493: Analysis of the Impact of Range and Setup Uncertainties On the Dose to Brain Stem and Whole Brain in the Passively Scattered Proton Therapy Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahoo, N; Zhu, X; Zhang, X

Purpose: To quantify the impact of range and setup uncertainties on various dosimetric indices that are used to assess normal tissue toxicities of patients receiving passive scattering proton beam therapy (PSPBT). Methods: Robust analysis of sample treatment plans of six brain cancer patients treated with PSPBT at our facility for whom the maximum brain stem dose exceeded 5800 CcGE were performed. The DVH of each plan was calculated in an Eclipse treatment planning system (TPS) version 11 applying ±3.5% range uncertainty and ±3 mm shift of the isocenter in x, y and z directions to account for setup uncertainties. Worst-casemore » dose indices for brain stem and whole brain were compared to their values in the nominal plan to determine the average change in their values. For the brain stem, maximum dose to 1 cc of volume, dose to 10%, 50%, 90% of volume (D10, D50, D90) and volume receiving 6000, 5400, 5000, 4500, 4000 CcGE (V60, V54, V50, V45, V40) were evaluated. For the whole brain, maximum dose to 1 cc of volume, and volume receiving 5400, 5000, 4500, 4000, 3000 CcGE (V54, V50, V45, V40 and V30) were assessed. Results: The average change in the values of these indices in the worst scenario cases from the nominal plan were as follows. Brain stem; Maximum dose to 1 cc of volume: 1.1%, D10: 1.4%, D50: 8.0%, D90:73.3%, V60:116.9%, V54:27.7%, V50: 21.2%, V45:16.2%, V40:13.6%,Whole brain; Maximum dose to 1 cc of volume: 0.3%, V54:11.4%, V50: 13.0%, V45:13.6%, V40:14.1%, V30:13.5%. Conclusion: Large to modest changes in the dosiemtric indices for brain stem and whole brain compared to nominal plan due to range and set up uncertainties were observed. Such potential changes should be taken into account while using any dosimetric parameters for outcome evaluation of patients receiving proton therapy.« less

Computerized ultrasound risk evaluation system

DOEpatents

Duric, Nebojsa; Littrup, Peter J.; Holsapple, III, Earle; Barter, Robert Henry; Moore, Thomas L.; Azevedo, Stephen G.; Ferguson, Sidney W.

2007-10-23

A method and system for examining tissue are provided in which the tissue is maintained in a position so that it may be insonified with a plurality of pulsed spherical or cylindrical acoustic waves. The insonifying acoustic waves are scattered by the tissue so that scattered acoustic radiation including a mix of reflected and transmitted acoustic waves is received. A representation of a portion of the tissue is then derived from the received scattered acoustic radiation.

Optical diagnostics based on elastic scattering: An update of clinical demonstrations with the Optical Biopsy System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bigio, I.J.; Boyer, J.; Johnson, T.M.

1994-10-01

The Los Alamos National Laboratory has continued the development of the Optical Biopsy System (OBS) for noninvasive, real-time in situ diagnosis of tissue pathologies. Our clinical studies have expanded since the last Biomedical Optics Europe conference (Budapest, September 1993), and we report here on the latest results of clinical tests in gastrointestinal tract. The OBS invokes a unique approach to optical diagnosis of tissue pathologies based on the elastic scattering properties, over a wide range of wavelengths, of the tissue. The use of elastic scattering as the key to optical tissue diagnostics in the OBS is based on the factmore » that many tissue pathologies, including a majority of cancer forms, manifest significant architectural changes at the cellular and sub-cellular level. Since the cellular components that cause elastic scattering have dimensions typically on the order of visible to near-IR wavelengths, the elastic (Mie) scattering properties will be wavelength dependent. Thus, morphology and size changes can be expected to cause significant changes in an optical signature that is derived from the wavelength-dependence of elastic scattering. The OBS employs a small fiberoptic probe that is amenable to use with any endoscope or catheter, or to direct surface examination. The probe is designed to be used in optical contact with the tissue under examination and has separate illuminating and collecting fibers. Thus, the light that is collected and transmitted to the analyzing spectrometer must first scatter through a small volume of the tissue before entering the collection fiber(s). Consequently, the system is also sensitive to the optical absorption spectrum of the tissue, over an effective operating range of <300 to 950 nm, and such absorption adds valuable complexity to the scattering spectral signature.« less

TU-G-210-01: Modeling for Breast and Brain HIFU Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christensen, D.

Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such asmore » the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)« less

Characterization of the Optical Properties of Turbid Media by Supervised Learning of Scattering Patterns.

PubMed

Hassaninia, Iman; Bostanabad, Ramin; Chen, Wei; Mohseni, Hooman

2017-11-10

Fabricated tissue phantoms are instrumental in optical in-vitro investigations concerning cancer diagnosis, therapeutic applications, and drug efficacy tests. We present a simple non-invasive computational technique that, when coupled with experiments, has the potential for characterization of a wide range of biological tissues. The fundamental idea of our approach is to find a supervised learner that links the scattering pattern of a turbid sample to its thickness and scattering parameters. Once found, this supervised learner is employed in an inverse optimization problem for estimating the scattering parameters of a sample given its thickness and scattering pattern. Multi-response Gaussian processes are used for the supervised learning task and a simple setup is introduced to obtain the scattering pattern of a tissue sample. To increase the predictive power of the supervised learner, the scattering patterns are filtered, enriched by a regressor, and finally characterized with two parameters, namely, transmitted power and scaled Gaussian width. We computationally illustrate that our approach achieves errors of roughly 5% in predicting the scattering properties of many biological tissues. Our method has the potential to facilitate the characterization of tissues and fabrication of phantoms used for diagnostic and therapeutic purposes over a wide range of optical spectrum.

Selective sensitivity of Mueller imaging for tissue scattering over absorption changes in cancer mimicking phantoms

NASA Astrophysics Data System (ADS)

Fathima, Adeeba; Sharma B. S., Mahima; N., Sujatha

2018-03-01

Tissue characterization using optical polarimetry, especially Mueller imaging is receiving sustained interest due to its potential in achieving optical contrast between normal and malignant variations. This is particularly important in identifying the margin of malignant growth in suspected tissue regions for accurate surgical removal, or in aiding the sampling procedure during biopsy. The sensitivity of Mueller matrix derived depolarization index to the combined effects of changes in scattering and absorption occurring in a cancerous growth is illustrated in this study. Depolarization imaging is shown to be useful in demarcating the boundary of two regions of differing optical properties using a tissue phantom, modeled according to the changes expected during cancerous growth in tissue. Tissue scattering and absorption are expected to generally increase with the nuclear size change and crowding as well as angiogenesis associated with malignancy. We have observed that there is selective sensitivity for the Mueller elements and derived depolarization index to tissue scattering over absorption in the object field. Although the scattering and absorption are expected to increase and decrease depolarization respectively, the optical contrast of Mueller images and the derived depolarization index between normal and cancerous tissue is found appreciable in this region.

Recovering refractive index correlation function from measurement of tissue scattering phase function (Conference Presentation)

NASA Astrophysics Data System (ADS)

Rogers, Jeremy D.

2016-03-01

Numerous methods have been developed to quantify the light scattering properties of tissue. These properties are of interest in diagnostic and screening applications due to sensitivity to changes in tissue ultrastructure and changes associated with disease such as cancer. Tissue is considered a weak scatterer because that the mean free path is much larger than the correlation length. When this is the case, all scattering properties can be calculated from the refractive index correlation function Bn(r). Direct measurement of Bn(r) is challenging because it requires refractive index measurement at high resolution over a large tissue volume. Instead, a model is usually assumed. One particularly useful model, the Whittle-Matern function includes several realistic function types such as mass fractal and exponential. Optical scattering properties for weakly scattering media can be determined analytically from Bn(r) by applying the Rayleigh-Gans-Debye (RGD) or Born Approximation, and so measured scattering properties are used to fit parameters of the model function. Direct measurement of Bn(r) would provide confirmation that the function is a good representation of tissue or help in identifying the length scale at which changes occur. The RGD approximation relates the scattering phase function to the refractive index correlation function through a Fourier transform. This can be inverted without approximation, so goniometric measurement of the scattering can be converted to Bn(r). However, geometric constraints of the measurement of the phase function, angular resolution, and wavelength result in a band limited measurement of Bn(r). These limits are discussed and example measurements are described.

Feasibility study of hidden flow imaging based on laser speckle technique using multiperspectives contrast images

NASA Astrophysics Data System (ADS)

Abookasis, David; Moshe, Tomer

2014-11-01

This paper demonstrates the insertion of lens array in the front of a CCD camera in a laser speckle imaging (LSI) like-technique to acquire multiple speckle reflectance projections for imaging blood flow in an intact biological tissue. In some of LSI applications, flow imaging is obtained by thinning or removing of the upper tissue layers to access blood vessels. In contrast, with the proposed approach flow imaging can be achieved while the tissue is intact. In the system, each lens from an hexagonal lens array observed the sample from slightly different perspectives and captured with a CCD camera. In the computer, these multiview raw images are converted to speckled contrast maps. Then, a self-deconvolution shift-and-add algorithm is employed for processing yields high contrast flow information. The method is experimentally validated first with a plastic tube filled with scattering liquid running at different controlled flow rates hidden in a biological tissue and then extensively tested for imaging of cerebral blood flow in an intact rodent head experience different conditions. A total of fifteen mice were used in the experiments divided randomly into three groups as follows: Group 1 (n=5) consisted of injured mice experience hypoxic ischemic brain injury monitored for ~40 min. Group 2 (n=5) injured mice experience anoxic brain injury monitored up to 20 min. Group 3 (n=5) experience functional activation monitored up to ~35 min. To increase tissue transparency and the penetration depth of photons through head tissue layers, an optical clearing method was employed. To our knowledge, this work presents for the first time the use of lens array in LSI scheme.

Fully iterative scatter corrected digital breast tomosynthesis using GPU-based fast Monte Carlo simulation and composition ratio update

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Kyungsang; Ye, Jong Chul, E-mail: jong.ye@kaist.ac.kr; Lee, Taewon

2015-09-15

Purpose: In digital breast tomosynthesis (DBT), scatter correction is highly desirable, as it improves image quality at low doses. Because the DBT detector panel is typically stationary during the source rotation, antiscatter grids are not generally compatible with DBT; thus, a software-based scatter correction is required. This work proposes a fully iterative scatter correction method that uses a novel fast Monte Carlo simulation (MCS) with a tissue-composition ratio estimation technique for DBT imaging. Methods: To apply MCS to scatter estimation, the material composition in each voxel should be known. To overcome the lack of prior accurate knowledge of tissue compositionmore » for DBT, a tissue-composition ratio is estimated based on the observation that the breast tissues are principally composed of adipose and glandular tissues. Using this approximation, the composition ratio can be estimated from the reconstructed attenuation coefficients, and the scatter distribution can then be estimated by MCS using the composition ratio. The scatter estimation and image reconstruction procedures can be performed iteratively until an acceptable accuracy is achieved. For practical use, (i) the authors have implemented a fast MCS using a graphics processing unit (GPU), (ii) the MCS is simplified to transport only x-rays in the energy range of 10–50 keV, modeling Rayleigh and Compton scattering and the photoelectric effect using the tissue-composition ratio of adipose and glandular tissues, and (iii) downsampling is used because the scatter distribution varies rather smoothly. Results: The authors have demonstrated that the proposed method can accurately estimate the scatter distribution, and that the contrast-to-noise ratio of the final reconstructed image is significantly improved. The authors validated the performance of the MCS by changing the tissue thickness, composition ratio, and x-ray energy. The authors confirmed that the tissue-composition ratio estimation was quite accurate under a variety of conditions. Our GPU-based fast MCS implementation took approximately 3 s to generate each angular projection for a 6 cm thick breast, which is believed to make this process acceptable for clinical applications. In addition, the clinical preferences of three radiologists were evaluated; the preference for the proposed method compared to the preference for the convolution-based method was statistically meaningful (p < 0.05, McNemar test). Conclusions: The proposed fully iterative scatter correction method and the GPU-based fast MCS using tissue-composition ratio estimation successfully improved the image quality within a reasonable computational time, which may potentially increase the clinical utility of DBT.« less

TH-AB-209-12: Tissue Equivalent Phantom with Excised Human Tissue for Assessing Clinical Capabilities of Coherent Scatter Imaging Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albanese, K; Morris, R; Spencer, J

Purpose: Previously we reported the development of anthropomorphic tissue-equivalent scatter phantoms of the human breast. Here we present the first results from the scatter imaging of the tissue equivalent breast phantoms for breast cancer diagnosis. Methods: A breast phantom was designed to assess the capability of coded aperture coherent x-ray scatter imaging to classify different types of breast tissue (adipose, fibroglandular, tumor). The phantom geometry was obtained from a prone breast geometry scanned on a dedicated breast CT system. The phantom was 3D printed using the segmented DICOM breast CT data. The 3D breast phantom was filled with lard (asmore » a surrogate for adipose tissue) and scanned in different geometries alongside excised human breast tissues (obtained from lumpectomy and mastectomy procedures). The raw data were reconstructed using a model-based reconstruction algorithm and yielded the location and form factor (i.e., momentum transfer (q) spectrum) of the materials that were imaged. The measured material form factors were then compared to the ground truth measurements acquired by x-ray diffraction (XRD) imaging. Results: Our scatter imaging system was able to define the location and composition of the various materials and tissues within the phantom. Cancerous breast tissue was detected and classified through automated spectral matching and an 86% correlation threshold. The total scan time for the sample was approximately 10 minutes and approaches workflow times for clinical use in intra-operative or other diagnostic tasks. Conclusion: This work demonstrates the first results from an anthropomorphic tissue equivalent scatter phantom to characterize a coherent scatter imaging system. The functionality of the system shows promise in applications such as intra-operative margin detection or virtual biopsy in the diagnosis of breast cancer. Future work includes using additional patient-derived tissues (e.g., human fat), and modeling additional organs (e.g., lung).« less

In vivo three-photon imaging of deep cerebellum

NASA Astrophysics Data System (ADS)

Wang, Mengran; Wang, Tianyu; Wu, Chunyan; Li, Bo; Ouzounov, Dimitre G.; Sinefeld, David; Guru, Akash; Nam, Hyung-Song; Capecchi, Mario R.; Warden, Melissa R.; Xu, Chris

2018-02-01

We demonstrate three-photon microscopy (3PM) of mouse cerebellum at 1 mm depth by imaging both blood vessels and neurons. We compared 3PM and 2PM in the mouse cerebellum for imaging green (using excitation sources at 1300 nm and 920 nm, respectively) and red fluorescence (using excitation sources at 1680 nm and 1064 nm, respectively). 3PM enabled deeper imaging than 2PM because the use of longer excitation wavelength reduces the scattering in biological tissue and the higher order nonlinear excitation provides better 3D localization. To illustrate these two advantages quantitatively, we measured the signal decay as well as the signal-to-background ratio (SBR) as a function of depth. We performed 2-photon imaging from the brain surface all the way down to the area where the SBR reaches 1, while at the same depth, 3PM still has SBR above 30. The segmented decay curve shows that the mouse cerebellum has different effective attenuation lengths at different depths, indicating heterogeneous tissue property for this brain region. We compared the third harmonic generation (THG) signal, which is used to visualize myelinated fibers, with the decay curve. We found that the regions with shorter effective attenuation lengths correspond to the regions with more fibers. Our results indicate that the widespread, non-uniformly distributed myelinated fibers adds heterogeneity to mouse cerebellum, which poses additional challenges in deep imaging of this brain region.

Wide-field high spatial frequency domain imaging of tissue microstructure

NASA Astrophysics Data System (ADS)

Lin, Weihao; Zeng, Bixin; Cao, Zili; Zhu, Danfeng; Xu, M.

2018-02-01

Wide-field tissue imaging is usually not capable of resolving tissue microstructure. We present High Spatial Frequency Domain Imaging (HSFDI) - a noncontact imaging modality that spatially maps the tissue microscopic scattering structures over a large field of view. Based on an analytical reflectance model of sub-diffusive light from forward-peaked highly scattering media, HSFDI quantifies the spatially-resolved parameters of the light scattering phase function from the reflectance of structured light modulated at high spatial frequencies. We have demonstrated with ex vivo cancerous tissue to validate the robustness of HSFDI in significant contrast and differentiation of the microstructutral parameters between different types and disease states of tissue.

Absorption and scattering coefficient dependence of laser-Doppler flowmetry models for large tissue volumes.

PubMed

Binzoni, T; Leung, T S; Rüfenacht, D; Delpy, D T

2006-01-21

Based on quasi-elastic scattering theory (and random walk on a lattice approach), a model of laser-Doppler flowmetry (LDF) has been derived which can be applied to measurements in large tissue volumes (e.g. when the interoptode distance is >30 mm). The model holds for a semi-infinite medium and takes into account the transport-corrected scattering coefficient and the absorption coefficient of the tissue, and the scattering coefficient of the red blood cells. The model holds for anisotropic scattering and for multiple scattering of the photons by the moving scatterers of finite size. In particular, it has also been possible to take into account the simultaneous presence of both Brownian and pure translational movements. An analytical and simplified version of the model has also been derived and its validity investigated, for the case of measurements in human skeletal muscle tissue. It is shown that at large optode spacing it is possible to use the simplified model, taking into account only a 'mean' light pathlength, to predict the blood flow related parameters. It is also demonstrated that the 'classical' blood volume parameter, derived from LDF instruments, may not represent the actual blood volume variations when the investigated tissue volume is large. The simplified model does not need knowledge of the tissue optical parameters and thus should allow the development of very simple and cost-effective LDF hardware.

Near-infrared spectroscopic tissue imaging for medical applications

DOEpatents

Demos,; Stavros, Staggs [Livermore, CA; Michael, C [Tracy, CA

2006-03-21

Near infrared imaging using elastic light scattering and tissue autofluorescence are explored for medical applications. The approach involves imaging using cross-polarized elastic light scattering and tissue autofluorescence in the Near Infra-Red (NIR) coupled with image processing and inter-image operations to differentiate human tissue components.

Near-infrared spectroscopic tissue imaging for medical applications

DOEpatents

Demos, Stavros [Livermore, CA; Staggs, Michael C [Tracy, CA

2006-12-12

Near infrared imaging using elastic light scattering and tissue autofluorescence are explored for medical applications. The approach involves imaging using cross-polarized elastic light scattering and tissue autofluorescence in the Near Infra-Red (NIR) coupled with image processing and inter-image operations to differentiate human tissue components.

An empirical approach to estimate near-infra-red photon propagation and optically induced drug release in brain tissues

NASA Astrophysics Data System (ADS)

Prabhu Verleker, Akshay; Fang, Qianqian; Choi, Mi-Ran; Clare, Susan; Stantz, Keith M.

2015-03-01

The purpose of this study is to develop an alternate empirical approach to estimate near-infra-red (NIR) photon propagation and quantify optically induced drug release in brain metastasis, without relying on computationally expensive Monte Carlo techniques (gold standard). Targeted drug delivery with optically induced drug release is a noninvasive means to treat cancers and metastasis. This study is part of a larger project to treat brain metastasis by delivering lapatinib-drug-nanocomplexes and activating NIR-induced drug release. The empirical model was developed using a weighted approach to estimate photon scattering in tissues and calibrated using a GPU based 3D Monte Carlo. The empirical model was developed and tested against Monte Carlo in optical brain phantoms for pencil beams (width 1mm) and broad beams (width 10mm). The empirical algorithm was tested against the Monte Carlo for different albedos along with diffusion equation and in simulated brain phantoms resembling white-matter (μs'=8.25mm-1, μa=0.005mm-1) and gray-matter (μs'=2.45mm-1, μa=0.035mm-1) at wavelength 800nm. The goodness of fit between the two models was determined using coefficient of determination (R-squared analysis). Preliminary results show the Empirical algorithm matches Monte Carlo simulated fluence over a wide range of albedo (0.7 to 0.99), while the diffusion equation fails for lower albedo. The photon fluence generated by empirical code matched the Monte Carlo in homogeneous phantoms (R2=0.99). While GPU based Monte Carlo achieved 300X acceleration compared to earlier CPU based models, the empirical code is 700X faster than the Monte Carlo for a typical super-Gaussian laser beam.

Method and apparatus for determining fat content of tissue

DOEpatents

Weber, Thomas M.; Spletzer, Barry L.; Bryan, Jon R.; Dickey, Fred M.; Shagam, Richard N.; Gooris, Luc

2001-01-01

A method and apparatus for determining characteristics of tissue is disclosed. The method comprises supplying optical energy to a tissue and detecting at a plurality of locations consequent energy scattered by the tissue. Analysis of the scattered energy as taught herein provides information concerning the properties of the tissue, specifically information related to the fat and lean content and thickness of the tissue. The apparatus comprises a light source adapted to deliver optical energy to a tissue. A plurality of detectors can be mounted at different positions relative to the source to detect energy scattered by the tissue. A signal processor as taught herein can determine characteristics of the tissue from the signals from the detectors and locations of the detectors, specifically information related to the fat and lean content and thickness of the tissue.

Assessment of ultrasound modulation of near infrared light on the quantification of scattering coefficient.

PubMed

Singh, M Suheshkumar; Yalavarthy, Phaneendra K; Vasu, R M; Rajan, K

2010-07-01

To assess the effect of ultrasound modulation of near infrared (NIR) light on the quantification of scattering coefficient in tissue-mimicking biological phantoms. A unique method to estimate the phase of the modulated NIR light making use of only time averaged intensity measurements using a charge coupled device camera is used in this investigation. These experimental measurements from tissue-mimicking biological phantoms are used to estimate the differential pathlength, in turn leading to estimation of optical scattering coefficient. A Monte-Carlo model based numerical estimation of phase in lieu of ultrasound modulation is performed to verify the experimental results. The results indicate that the ultrasound modulation of NIR light enhances the effective scattering coefficient. The observed effective scattering coefficient enhancement in tissue-mimicking viscoelastic phantoms increases with increasing ultrasound drive voltage. The same trend is noticed as the ultrasound modulation frequency approaches the natural vibration frequency of the phantom material. The contrast enhancement is less for the stiffer (larger storage modulus) tissue, mimicking tumor necrotic core, compared to the normal tissue. The ultrasound modulation of the insonified region leads to an increase in the effective number of scattering events experienced by NIR light, increasing the measured phase, causing the enhancement in the effective scattering coefficient. The ultrasound modulation of NIR light could provide better estimation of scattering coefficient. The observed local enhancement of the effective scattering coefficient, in the ultrasound focal region, is validated using both experimental measurements and Monte-Carlo simulations.

Phase Contrast Microscopy Analysis of Breast Tissue

PubMed Central

Wells, Wendy A.; Wang, Xin; Daghlian, Charles P.; Paulsen, Keith D.; Pogue, Brian W.

2010-01-01

OBJECTIVE To assess how optical scatter properties in breast tissue, as measured by phase contrast microscopy and interpreted pathophysiologically, might be exploited as a diagnostic tool to differentiate cancer from benign tissue. STUDY DESIGN We evaluated frozen human breast tissue sections of adipose tissue, normal breast parenchyma, benign fibroadenoma tumors and noninvasive and invasive malignant cancers by phase contrast microscopy through quantification of grayscale values, using multiple regions of interest (ROI). Student’s t tests were performed on phase contrast measures across diagnostic categories testing data from individual cases; all ROI data were used as separate measures. RESULTS Stroma demonstrated significantly higher scatter intensity than did epithelium, with lower scattering in tumor-associated stroma as compared with normal or benign-associated stroma. Measures were comparable for invasive and noninvasive malignant tumors but were higher than those found in benign tumors and were lowest in adipose tissue. CONCLUSION Significant differences were found in scatter coefficient properties of epithelium and stroma across diagnostic categories of breast tissue, particularly between benign and malignant-associated stroma. Improved understanding of how scatter properties correlate with morphologic criteria used in routine pathologic diagnoses could have a significant clinical impact as developing optical technology allows macroscopic in situ phase contrast imaging. PMID:19736867

Dual-window dual-bandwidth spectroscopic optical coherence tomography metric for qualitative scatterer size differentiation in tissues.

PubMed

Tay, Benjamin Chia-Meng; Chow, Tzu-Hao; Ng, Beng-Koon; Loh, Thomas Kwok-Seng

2012-09-01

This study investigates the autocorrelation bandwidths of dual-window (DW) optical coherence tomography (OCT) k-space scattering profile of different-sized microspheres and their correlation to scatterer size. A dual-bandwidth spectroscopic metric defined as the ratio of the 10% to 90% autocorrelation bandwidths is found to change monotonically with microsphere size and gives the best contrast enhancement for scatterer size differentiation in the resulting spectroscopic image. A simulation model supports the experimental results and revealed a tradeoff between the smallest detectable scatterer size and the maximum scatterer size in the linear range of the dual-window dual-bandwidth (DWDB) metric, which depends on the choice of the light source optical bandwidth. Spectroscopic OCT (SOCT) images of microspheres and tonsil tissue samples based on the proposed DWDB metric showed clear differentiation between different-sized scatterers as compared to those derived from conventional short-time Fourier transform metrics. The DWDB metric significantly improves the contrast in SOCT imaging and can aid the visualization and identification of dissimilar scatterer size in a sample. Potential applications include the early detection of cell nuclear changes in tissue carcinogenesis, the monitoring of healing tendons, and cell proliferation in tissue scaffolds.

Analysis of the scattering performance of human retinal tissue layers

NASA Astrophysics Data System (ADS)

Zhu, Dan; Gao, Zhisan; Ye, Haishui; Yuan, Qun

2017-02-01

Human retina is different from other ocular tissues, such as cornea, crystalline lens and vitreous because of high scattering performance. As an anisotropic tissue, we cannot neglect its impact on the polarization state of the scattered light. In this paper, Mie scattering and radiative transfer theory are applied to analyze the polarization state of backscattered light from four types of retinal tissues, including neural retina, retinal pigment epithelial (RPE), choroid and sclera. The results show that the most backscattered zones in different depths have almost the same electrical fields of Jones vector, which represents the polarization state of light, whether neural retina layer is under normal incidence or oblique incidence. Very little change occurs in the polarization of backscattered light compared to that of the incident light. Polarization distribution of backward scattered light from neural retina layer doesn't make apparent effects on polarization phase shifting in spectral domain OCT because its thickness is far less than photon mean free path, while other retinal tissues do not meet this rule.

Enhanced in-vivo optical coherence tomography of live mouse brain by the use of implanted micro-lens (Presentation Recording)

NASA Astrophysics Data System (ADS)

Hassani Nia, Iman; Dombeck, Daniel; Mohseni, Hooman

2015-08-01

Near-infrared optical coherence tomography (OCT) has gained a lot of attention due to the fact that it is relatively cheap, non-invasive and provides high resolution and fast method of imaging. However the main challenge of this technique is the poor signal to noise ratio of the images of the tissue at large depths due to optical scattering. The signal to noise ratio can be improved by increasing the source power, however the laser safety standards (ANSI Z136.1) restricts the maximum amount of power that can be used safely to characterize the biological tissue. In this talk, we discuss the advantage of implanting a micro-lens inside the tissue to have a higher signal to noise ratio for confocal and OCT measurements. We explain the theoretical background, experimental setup and the method of implanting the micro lens at arbitrary depths within a live mouse brain. The in-vivo 3D OCT and two-photon microscopy images of live mouse with implanted micro-lens are presented and significant enhancement of signal to noise ratio is observed. The confocal and OCT measurements have been performed with super-luminescent LEDs emitting at 1300 nm. We believe that the high resolution and high sensitivity of this technique is of fundamental importance for characterization of neural activity, monitoring the hemodynamic responses, tumors and for performing image guided surgeries.

Banking brain tissue for research.

PubMed

Klioueva, Natasja; Bovenberg, Jasper; Huitinga, Inge

2017-01-01

Well-characterized human brain tissue is crucial for scientific breakthroughs in research of the human brain and brain diseases. However, the collection, characterization, management, and accessibility of brain human tissue are rather complex. Well-characterized human brain tissue is often provided from private, sometimes small, brain tissue collections by (neuro)pathologic experts. However, to meet the increasing demand for human brain tissue from the scientific community, many professional brain-banking activities aiming at both neurologic and psychiatric diseases as well as healthy controls are currently being initiated worldwide. Professional biobanks are open-access and in many cases run donor programs. They are therefore costly and need effective business plans to guarantee long-term sustainability. Here we discuss the ethical, legal, managerial, and financial aspects of professional brain banks. Copyright © 2017 Elsevier B.V. All rights reserved.

Relation between speckle decorrelation and optical phase conjugation (OPC)-based turbidity suppression through dynamic scattering media: a study on in vivo mouse skin.

PubMed

Jang, Mooseok; Ruan, Haowen; Vellekoop, Ivo M; Judkewitz, Benjamin; Chung, Euiheon; Yang, Changhuei

2015-01-01

Light scattering in biological tissue significantly limits the accessible depth for localized optical interrogation and deep-tissue optical imaging. This challenge can be overcome by exploiting the time-reversal property of optical phase conjugation (OPC) to reverse multiple scattering events or suppress turbidity. However, in living tissue, scatterers are highly movable and the movement can disrupt time-reversal symmetry when there is a latency in the OPC playback. In this paper, we show that the motion-induced degradation of the OPC turbidity-suppression effect through a dynamic scattering medium shares the same decorrelation time constant as that determined from speckle intensity autocorrelation - a popular conventional measure of scatterer movement. We investigated this decorrelation characteristic time through a 1.5-mm-thick dorsal skin flap of a living mouse and found that it ranges from 50 ms to 2.5 s depending on the level of immobilization. This study provides information on relevant time scales for applying OPC to living tissues.

Tissue structure characterization of biotissue phantom by use of the speckle-correlometric technique

NASA Astrophysics Data System (ADS)

Isaeva, A. A.; Isaeva, E. A.; Zimnyakov, D. A.; Pantyukov, A. V.; Agapova, Y. V.; Macheyev, M. A.

2017-03-01

Speckle correlometry gives the possibilities to visualize tissue scattering structure analyzing the correlation characteristics of speckle-modulated images. In this work, the inhomogeneous multiple scattering medium with the "dynamic" long inclusions was investigated like a blood vessels in living tissue. The scattering media is 0.28% weight fraction of gelatin dissolved in water and 1 gram per liter (gL-1) and 100 mg per liter (gL-1) of TiO2 for optical scattering. The movement of fluid (distilled water) in the cylindrical hole with given radius simulate a blood motion in the vessel. It was shown the possibility to determinate the depth location of dynamic inhomogeneities inside a scattering medium.

Fiber-array based optogenetic prosthetic system for stimulation therapy

NASA Astrophysics Data System (ADS)

Gu, Ling; Cote, Chris; Tejeda, Hector; Mohanty, Samarendra

2012-02-01

Recent advent of optogenetics has enabled activation of genetically-targeted neuronal cells using low intensity blue light with high temporal precision. Since blue light is attenuated rapidly due to scattering and absorption in neural tissue, optogenetic treatment of neurological disorders may require stimulation of specific cell types in multiple regions of the brain. Further, restoration of certain neural functions (vision, and auditory etc) requires accurate spatio-temporal stimulation patterns rather than just precise temporal stimulation. In order to activate multiple regions of the central nervous system in 3D, here, we report development of an optogenetic prosthetic comprising of array of fibers coupled to independently-controllable LEDs. This design avoids direct contact of LEDs with the brain tissue and thus does not require electrical and heat isolation, which can non-specifically stimulate and damage the local brain regions. The intensity, frequency, and duty cycle of light pulses from each fiber in the array was controlled independently using an inhouse developed LabView based program interfaced with a microcontroller driving the individual LEDs. While the temporal profile of the light pulses was controlled by varying the current driving the LED, the beam profile emanating from each fiber tip could be sculpted by microfabrication of the fiber tip. The fiber array was used to stimulate neurons, expressing channelrhodopsin-2, in different locations within the brain or retina. Control of neural activity in the mice cortex, using the fiber-array based prosthetic, is evaluated from recordings made with multi-electrode array (MEA). We also report construction of a μLED array based prosthetic for spatio-temporal stimulation of cortex.

Non-scanning fiber-optic near-infrared beam led to two-photon optogenetic stimulation in-vivo.

PubMed

Dhakal, Kamal R; Gu, Ling; Shivalingaiah, Shivaranjani; Dennis, Torry S; Morris-Bobzean, Samara A; Li, Ting; Perrotti, Linda I; Mohanty, Samarendra K

2014-01-01

Stimulation of specific neurons expressing opsins in a targeted region to manipulate brain function has proved to be a powerful tool in neuroscience. However, the use of visible light for optogenetic stimulation is invasive due to low penetration depth and tissue damage owing to larger absorption and scattering. Here, we report, for the first time, in-depth non-scanning fiber-optic two-photon optogenetic stimulation (FO-TPOS) of neurons in-vivo in transgenic mouse models. In order to optimize the deep-brain stimulation strategy, we characterized two-photon activation efficacy at different near-infrared laser parameters. The significantly-enhanced in-depth stimulation efficiency of FO-TPOS as compared to conventional single-photon beam was demonstrated both by experiments and Monte Carlo simulation. The non-scanning FO-TPOS technology will lead to better understanding of the in-vivo neural circuitry because this technology permits more precise and less invasive anatomical delivery of stimulation.

Non-invasive monitoring of hemodynamic changes in orthotropic brain tumor

NASA Astrophysics Data System (ADS)

Kashyap, Dheerendra; Sharma, Vikrant; Liu, Hanli

2007-02-01

Radio surgical interventions such as Gamma Knife and Cyberknife have become attractive as therapeutic interventions. However, one of the drawbacks of cyberknife is radionecrosis, which is caused by excessive radiation to surrounding normal tissues. Radionecrosis occurs in about 10-15% of cases and could have adverse effects leading to death. Currently available imaging techniques have failed to reliably distinguish radionecrosis from tumor growth. Development of imaging techniques that could provide distinction between tumor growth and radionecrosis would give us ability to monitor effects of radiation therapy non-invasively. This paper investigates the use of near infrared spectroscopy (NIRS) as a new technique to monitor the growth of brain tumors. Brain tumors (9L glioma cell line) were implanted in right caudate nucleus of rats (250-300 gms, Male Fisher C) through a guide screw. A new algorithm was developed, which used broadband steady-state reflectance measurements made using a single source-detector pair, to quantify absolute concentrations of hemoglobin derivatives and reduced scattering coefficients. Preliminary results from the brain tumors indicated decreases in oxygen saturation, oxygenated hemoglobin concentrations and increases in deoxygenated hemoglobin concentrations with tumor growth. The study demonstrates that NIRS technology could provide an efficient, noninvasive means of monitoring vascular oxygenation dynamics of brain tumors and further facilitate investigations of efficacy of tumor treatments.

Effect of vitro preservation on mechanical properties of brain tissue

NASA Astrophysics Data System (ADS)

Zhang, Wei; Liu, Yi-fan; Liu, Li-fu; Niu, Ying; Ma, Jian-li; Wu, Cheng-wei

2017-05-01

To develop the protective devices for preventing traumatic brain injuries, it requires the accurate characterization of the mechanical properties of brain tissue. For this, it necessary to elucidate the effect of vitro preservation on the mechanical performance of brain tissue as usually the measurements are carried out in vitro. In this paper, the thermal behavior of brain tissue preserved for various period of time was first investigated and the mechanical properties were also measured. Both reveals the deterioration with prolonged preservation duration. The observations of brain tissue slices indicates the brain tissue experiences karyorrhexis and karyorrhexis in sequence, which accounts for the deterioration phenomena.

Theoretical evaluation of accuracy in position and size of brain activity obtained by near-infrared topography

NASA Astrophysics Data System (ADS)

Kawaguchi, Hiroshi; Hayashi, Toshiyuki; Kato, Toshinori; Okada, Eiji

2004-06-01

Near-infrared (NIR) topography can obtain a topographical distribution of the activated region in the brain cortex. Near-infrared light is strongly scattered in the head, and the volume of tissue sampled by a source-detector pair on the head surface is broadly distributed in the brain. This scattering effect results in poor resolution and contrast in the topographic image of the brain activity. In this study, a one-dimensional distribution of absorption change in a head model is calculated by mapping and reconstruction methods to evaluate the effect of the image reconstruction algorithm and the interval of measurement points for topographic imaging on the accuracy of the topographic image. The light propagation in the head model is predicted by Monte Carlo simulation to obtain the spatial sensitivity profile for a source-detector pair. The measurement points are one-dimensionally arranged on the surface of the model, and the distance between adjacent measurement points is varied from 4 mm to 28 mm. Small intervals of the measurement points improve the topographic image calculated by both the mapping and reconstruction methods. In the conventional mapping method, the limit of the spatial resolution depends upon the interval of the measurement points and spatial sensitivity profile for source-detector pairs. The reconstruction method has advantages over the mapping method which improve the results of one-dimensional analysis when the interval of measurement points is less than 12 mm. The effect of overlapping of spatial sensitivity profiles indicates that the reconstruction method may be effective to improve the spatial resolution of a two-dimensional reconstruction of topographic image obtained with larger interval of measurement points. Near-infrared topography with the reconstruction method potentially obtains an accurate distribution of absorption change in the brain even if the size of absorption change is less than 10 mm.

Modeling ultrasonic transient scattering from biological tissues including their dispersive properties directly in the time domain.

PubMed

Norton, G V; Novarini, J C

2007-06-01

Ultrasonic imaging in medical applications involves propagation and scattering of acoustic waves within and by biological tissues that are intrinsically dispersive. Analytical approaches for modeling propagation and scattering in inhomogeneous media are difficult and often require extremely simplifying approximations in order to achieve a solution. To avoid such approximations, the direct numerical solution of the wave equation via the method of finite differences offers the most direct tool, which takes into account diffraction and refraction. It also allows for detailed modeling of the real anatomic structure and combination/layering of tissues. In all cases the correct inclusion of the dispersive properties of the tissues can make the difference in the interpretation of the results. However, the inclusion of dispersion directly in the time domain proved until recently to be an elusive problem. In order to model the transient signal a convolution operator that takes into account the dispersive characteristics of the medium is introduced to the linear wave equation. To test the ability of this operator to handle scattering from localized scatterers, in this work, two-dimensional numerical modeling of scattering from an infinite cylinder with physical properties associated with biological tissue is calculated. The numerical solutions are compared with the exact solution synthesized from the frequency domain for a variety of tissues having distinct dispersive properties. It is shown that in all cases, the use of the convolutional propagation operator leads to the correct solution for the scattered field.

ON THE BENEFITS AND RISKS OF PROTON THERAPY IN PEDIATRIC CRANIOPHARYNGIOMA

PubMed Central

Beltran, Chris; Roca, Monica; Merchant, Thomas E.

2013-01-01

Purpose Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients. Methods and Materials For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.1 years) irradiated with photons (54 Gy) and monitored by weekly magnetic resonance imaging (MRI) examinations during radiation therapy. Photon intensity-modulated radiation therapy (IMRT), double-scatter proton (DSP) therapy, and intensity-modulated proton therapy (IMPT) plans were created for each patient based on his or her pre-irradiation MRI. Target volumes were contoured on each weekly MRI scan for adaptive modeling. The measured differences in conformity index (CI) and normal tissue doses, including functional sub-volumes of the brain, were compared across the planning methods, as was target coverage based on changes in target volumes during treatment. Results CI and normal tissue dose values of IMPT plans were significantly better than those of the IMRT and DSP plans (p < 0.01). Although IMRT plans had a higher CI and lower optic nerve doses (p < 0.01) than did DSP plans, DSP plans had lower cochlear, optic chiasm, brain, and scanned body doses (p < 0.01). The mean planning target volume (PTV) at baseline was 54.8 cm3, and the mean increase in PTV was 11.3% over the course of treatment. The dose to 95% of the PTV was correlated with a change in the PTV; the R2 values for all models, 0.73 (IMRT), 0.38 (DSP), and 0.62 (IMPT), were significant (p < 0.01). Conclusions Compared with photon IMRT, proton therapy has the potential to significantly reduce whole-brain and -body irradiation in pediatric patients with craniopharyngioma. IMPT is the most conformal method and spares the most normal tissue; however, it is highly sensitive to target volume changes, whereas the DSP method is not. PMID:21570209

Whole field reflectance optical tomography

NASA Astrophysics Data System (ADS)

Carbone, Nicolás A.; García, Héctor A.; di Rocco, Héctor O.; Iriarte, Daniela I.; Pomarico, Juan A.; Ranea Sandoval, Héctor F.

2011-08-01

Optical imaging through highly scattering media such as biological tissues is a topic of intense research, especially for biomedical applications. Diverse optical systems are currently under study and development for displaying the functional imaging of the brain and for the detection of breast tumors. From the theoretical point of view, a suitable description of light propagation in tissues involves the Radiative Transfer Equation, which considers the energetic aspects of light propagation. However, this equation cannot be solved analytically in a closed form and the Diffusion Approximation is normally used. Experimentally it is possible to use Transmission or Reflection geometries and Time Resolved, Frequency Modulated or CW sources. Each configuration has specific advantages and drawbacks, depending on the desired application. In the present contribution, we investigate the reflected light images registered by a CCD camera when scattering and absorbing inhomogeneities are located at different depths inside turbid media. This configuration is of particular interest for the detection and optical characterization of changes in blood flow in organs, as well as for the detection and characterization of inclusions in those cases for which the transmission slab geometry is not well suited. Images are properly normalized to the background intensity and allow analyzing relative large areas (typically 5 × 5 cm2) of the tissue. We tested the proposal using Numerical Monte Carlo simulations implemented in a Graphic Processing Unit (Video accelerating Card). Calculations are thus several orders of magnitude faster than those run in CPU. Experimental results in phantoms are also given.

The influence of the blood vessel diameter on the full scattering profile from cylindrical tissues: experimental evidence for the shielding effect.

PubMed

Feder, Idit; Duadi, Hamootal; Dreifuss, Tamar; Fixler, Dror

2016-10-01

Optical methods for detecting physiological state based on light-tissue interaction are noninvasive, inexpensive, simplistic, and thus very useful. The blood vessels in human tissue are the main cause of light absorbing and scattering. Therefore, the effect of blood vessels on light-tissue interactions is essential for optically detecting physiological tissue state, such as oxygen saturation, blood perfusion and blood pressure. We have previously suggested a new theoretical and experimental method for measuring the full scattering profile, which is the angular distribution of light intensity, of cylindrical tissues. In this work we will present experimental measurements of the full scattering profile of heterogenic cylindrical phantoms that include blood vessels. We show, for the first time that the vessel diameter influences the full scattering profile, and found higher reflection intensity for larger vessel diameters accordance to the shielding effect. For an increase of 60% in the vessel diameter the light intensity in the full scattering profile above 90° is between 9% to 40% higher, depending on the angle. By these results we claim that during respiration, when the blood-vessel diameter changes, it is essential to consider the blood-vessel diameter distribution in order to determine the optical path in tissues. A CT scan of the measured silicon-based phantoms. The phantoms contain the same blood volume in different blood-vessel diameters. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A new biomedical device for in vivo multiparametric evaluation of tissue vitality in critical care medicine

NASA Astrophysics Data System (ADS)

Mayevsky, Avraham; Deutsch, Assaf; Dekel, Nava; Pevzner, Eliyahu; Jaronkin, Alex

2005-04-01

Real time Monitoring of mitochondrial function in vivo is a significant factor in the understanding of tissue vitality. Nevertheless a single parameter monitoring device is not appropriate and effective in clinical diagnosis of tissue vitality. Therefore we have developed a multi-parametric monitoring system that monitors, in addition to mitochondrial NADH redox state, tissue microcirculatory blood flow, tissue total back-scattered light as an indication of blood volume and blood oxygenation (Hb02). In the present communication a new device named "CritiView" is described. This device was developed in order to enable real time monitoring of the four parameters from various organs in the body. The main medical application of the CritiView is in critical care medicine of patients hospitalized in the Intensive Care Units (ICUs) and intraoperatively in operating rooms. The physiological basis for our clinical monitoring approach is based on the well known response to the development of body emergency situation, such as shock or trauma. Under such conditions a process of blood flow redistribution will give preference to vital organs (Brain, Heart) neglecting less vital organs (Skin, G-I tract or the urinary system). Under such condition the brain will by hyperperfused and O2 supply will increase to provide the need of the activated mitochondria. The non-vital organs will be hypoperfused and mitochondial function will be inhibited leading to energy failure. This differentiation between the two types of organs could be used for the early detection of body deterioration by monitoring of the non-vital organ vitality. A fiber optic sensor was embedded in a Foley catheter, enabling the monitoring of Urethral wall vitality, to serve as an early warning signal of body deterioration.

Light distribution properties in spinal cord for optogenetic stimulation (Conference Presentation)

NASA Astrophysics Data System (ADS)

GÄ secka, Alicja; Bahdine, Mohamed; Lapointe, Nicolas; Rioux, Veronique; Perez-Sanchez, Jimena; Bonin, Robert P.; De Koninck, Yves; Côté, Daniel

2016-03-01

Optogenetics is currently one of the most popular technique in neuroscience. It enables cell-selective and temporally-precise control of neuronal activity. Good spatial control of the stimulated area and minimized tissue damage requires a specific knowledge about light scattering properties. Light propagation in cell cultures and brain tissue is relatively well documented and allows for a precise and reliable delivery of light to the neurons. In spinal cord, light must pass through highly organized white matter before reaching cell bodies present in grey matter, this heterogenous structure makes it difficult to predict the propagation pattern. In this work we investigate the light distribution properties through mouse and monkey spinal cord. The light propagation depends on a fibers orientation, leading to less deep penetration profile in the direction perpendicular to the fibers and lower attenuation in the direction parallel to the fibers. Additionally, the use of different illumination wavelengths results in variations of the attenuation coefficient. Next, we use Monte-Carlo simulation to study light transport. The model gives a full 3-D simulation of light distribution in spinal cord and takes into account different scattering properties related to the fibers orientation. These studies are important to estimate the minimum optical irradiance required at the fiber tip to effectively excite the optogenetic proteins in a desired region of spinal cord.

Dual-slit confocal light sheet microscopy for in vivo whole-brain imaging of zebrafish

PubMed Central

Yang, Zhe; Mei, Li; Xia, Fei; Luo, Qingming; Fu, Ling; Gong, Hui

2015-01-01

In vivo functional imaging at single-neuron resolution is an important approach to visualize biological processes in neuroscience. Light sheet microscopy (LSM) is a cutting edge in vivo imaging technique that provides micron-scale spatial resolution at high frame rate. Due to the scattering and absorption of tissue, however, conventional LSM is inadequate to resolve cells because of the attenuated signal to noise ratio (SNR). Using dual-beam illumination and confocal dual-slit detection, here a dual-slit confocal LSM is demonstrated to obtain the SNR enhanced images with frame rate twice as high as line confocal LSM method. Through theoretical calculations and experiments, the correlation between the slit’s width and SNR was determined to optimize the image quality. In vivo whole brain structural imaging stacks and the functional imaging sequences of single slice were obtained for analysis of calcium activities at single-cell resolution. A two-fold increase in imaging speed of conventional confocal LSM makes it possible to capture the sequence of the neurons’ activities and help reveal the potential functional connections in the whole zebrafish’s brain. PMID:26137381

Polarized Raman spectroscopy of bone tissue: watch the scattering

NASA Astrophysics Data System (ADS)

Raghavan, Mekhala; Sahar, Nadder D.; Wilson, Robert H.; Mycek, Mary-Ann; Pleshko, Nancy; Kohn, David H.; Morris, Michael D.

2010-02-01

Polarized Raman spectroscopy is widely used in the study of molecular composition and orientation in synthetic and natural polymer systems. Here, we describe the use of Raman spectroscopy to extract quantitative orientation information from bone tissue. Bone tissue poses special challenges to the use of polarized Raman spectroscopy for measurement of orientation distribution functions because the tissue is turbid and birefringent. Multiple scattering in turbid media depolarizes light and is potentially a source of error. Using a Raman microprobe, we show that repeating the measurements with a series of objectives of differing numerical apertures can be used to assess the contributions of sample turbidity and depth of field to the calculated orientation distribution functions. With this test, an optic can be chosen to minimize the systematic errors introduced by multiple scattering events. With adequate knowledge of the optical properties of these bone tissues, we can determine if elastic light scattering affects the polarized Raman measurements.

Fabrication and characterization of a 3-D non-homogeneous tissue-like mouse phantom for optical imaging

NASA Astrophysics Data System (ADS)

Avtzi, Stella; Zacharopoulos, Athanasios; Psycharakis, Stylianos; Zacharakis, Giannis

2013-11-01

In vivo optical imaging of biological tissue not only requires the development of new theoretical models and experimental procedures, but also the design and construction of realistic tissue-mimicking phantoms. However, most of the phantoms available currently in literature or the market, have either simple geometrical shapes (cubes, slabs, cylinders) or when realistic in shape they use homogeneous approximations of the tissue or animal under investigation. The goal of this study is to develop a non-homogeneous realistic phantom that matches the anatomical geometry and optical characteristics of the mouse head in the visible and near-infrared spectral range. The fabrication of the phantom consisted of three stages. Initially, anatomical information extracted from either mouse head atlases or structural imaging modalities (MRI, XCT) was used to design a digital phantom comprising of the three main layers of the mouse head; the brain, skull and skin. Based on that, initial prototypes were manufactured by using accurate 3D printing, allowing complex objects to be built layer by layer with sub-millimeter resolution. During the second stage the fabrication of individual molds was performed by embedding the prototypes into a rubber-like silicone mixture. In the final stage the detailed phantom was constructed by loading the molds with epoxy resin of controlled optical properties. The optical properties of the resin were regulated by using appropriate quantities of India ink and intralipid. The final phantom consisted of 3 layers, each one with different absorption and scattering coefficient (μa,μs) to simulate the region of the mouse brain, skull and skin.

Characterizing optical properties and spatial heterogeneity of human ovarian tissue using spatial frequency domain imaging

NASA Astrophysics Data System (ADS)

Nandy, Sreyankar; Mostafa, Atahar; Kumavor, Patrick D.; Sanders, Melinda; Brewer, Molly; Zhu, Quing

2016-10-01

A spatial frequency domain imaging (SFDI) system was developed for characterizing ex vivo human ovarian tissue using wide-field absorption and scattering properties and their spatial heterogeneities. Based on the observed differences between absorption and scattering images of different ovarian tissue groups, six parameters were quantitatively extracted. These are the mean absorption and scattering, spatial heterogeneities of both absorption and scattering maps measured by a standard deviation, and a fitting error of a Gaussian model fitted to normalized mean Radon transform of the absorption and scattering maps. A logistic regression model was used for classification of malignant and normal ovarian tissues. A sensitivity of 95%, specificity of 100%, and area under the curve of 0.98 were obtained using six parameters extracted from the SFDI images. The preliminary results demonstrate the diagnostic potential of the SFDI method for quantitative characterization of wide-field optical properties and the spatial distribution heterogeneity of human ovarian tissue. SFDI could be an extremely robust and valuable tool for evaluation of the ovary and detection of neoplastic changes of ovarian cancer.

Energy-Looping Nanoparticles: Harnessing Excited-State Absorption for Deep-Tissue Imaging.

PubMed

Levy, Elizabeth S; Tajon, Cheryl A; Bischof, Thomas S; Iafrati, Jillian; Fernandez-Bravo, Angel; Garfield, David J; Chamanzar, Maysamreza; Maharbiz, Michel M; Sohal, Vikaas S; Schuck, P James; Cohen, Bruce E; Chan, Emory M

2016-09-27

Near infrared (NIR) microscopy enables noninvasive imaging in tissue, particularly in the NIR-II spectral range (1000-1400 nm) where attenuation due to tissue scattering and absorption is minimized. Lanthanide-doped upconverting nanocrystals are promising deep-tissue imaging probes due to their photostable emission in the visible and NIR, but these materials are not efficiently excited at NIR-II wavelengths due to the dearth of lanthanide ground-state absorption transitions in this window. Here, we develop a class of lanthanide-doped imaging probes that harness an energy-looping mechanism that facilitates excitation at NIR-II wavelengths, such as 1064 nm, that are resonant with excited-state absorption transitions but not ground-state absorption. Using computational methods and combinatorial screening, we have identified Tm(3+)-doped NaYF4 nanoparticles as efficient looping systems that emit at 800 nm under continuous-wave excitation at 1064 nm. Using this benign excitation with standard confocal microscopy, energy-looping nanoparticles (ELNPs) are imaged in cultured mammalian cells and through brain tissue without autofluorescence. The 1 mm imaging depths and 2 μm feature sizes are comparable to those demonstrated by state-of-the-art multiphoton techniques, illustrating that ELNPs are a promising class of NIR probes for high-fidelity visualization in cells and tissue.

Structural characterization of the human cerebral myelin sheath by small angle x-ray scattering

NASA Astrophysics Data System (ADS)

DeFelici, M.; Felici, R.; Ferrero, C.; Tartari, A.; Gambaccini, M.; Finet, S.

2008-10-01

Myelin is a multi-lamellar membrane surrounding neuronal axons and increasing their conduction velocity. When investigated by small-angle x-ray scattering (SAXS), the lamellar quasi-periodical arrangement of the myelin sheath gives rise to distinct peaks, which allow the determination of its molecular organization and the dimensions of its substructures. In this study we report on the myelin sheath structural determination carried out on a set of human brain tissue samples coming from surgical biopsies of two patients: a man around 60 and a woman nearly 90 years old. The samples were extracted either from white or grey cerebral matter and did not undergo any manipulation or chemical-physical treatment, which could possibly have altered their structure, except dipping them into a formalin solution for their conservation. Analysis of the scattered intensity from white matter of intact human cerebral tissue allowed the evaluation not only of the myelin sheath periodicity but also of its electronic charge density profile. In particular, the thicknesses of the cytoplasm and extracellular regions were established, as well as those of the hydrophilic polar heads and hydrophobic tails of the lipid bilayer. SAXS patterns were measured at several locations on each sample in order to establish the statistical variations of the structural parameters within a single sample and among different samples. This work demonstrates that a detailed structural analysis of the myelin sheath can also be carried out in randomly oriented samples of intact human white matter, which is of importance for studying the aetiology and evolution of the central nervous system pathologies inducing myelin degeneration.

A New Antigen Retrieval Technique for Human Brain Tissue

PubMed Central

Byne, William; Haroutunian, Vahram; García-Villanueva, Mercedes; Rábano, Alberto; García-Amado, María; Prensa, Lucía; Giménez-Amaya, José Manuel

2008-01-01

Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times. PMID:18852880

Relation between speckle decorrelation and optical phase conjugation (OPC)-based turbidity suppression through dynamic scattering media: a study on in vivo mouse skin

PubMed Central

Jang, Mooseok; Ruan, Haowen; Vellekoop, Ivo M.; Judkewitz, Benjamin; Chung, Euiheon; Yang, Changhuei

2014-01-01

Light scattering in biological tissue significantly limits the accessible depth for localized optical interrogation and deep-tissue optical imaging. This challenge can be overcome by exploiting the time-reversal property of optical phase conjugation (OPC) to reverse multiple scattering events or suppress turbidity. However, in living tissue, scatterers are highly movable and the movement can disrupt time-reversal symmetry when there is a latency in the OPC playback. In this paper, we show that the motion-induced degradation of the OPC turbidity-suppression effect through a dynamic scattering medium shares the same decorrelation time constant as that determined from speckle intensity autocorrelation – a popular conventional measure of scatterer movement. We investigated this decorrelation characteristic time through a 1.5-mm-thick dorsal skin flap of a living mouse and found that it ranges from 50 ms to 2.5 s depending on the level of immobilization. This study provides information on relevant time scales for applying OPC to living tissues. PMID:25657876

Method for measuring changes in light absorption of highly scattering media

DOEpatents

Bigio, Irving J.; Johnson, Tamara M.; Mourant, Judith R.

2002-01-01

The noninvasive measurement of variations in absorption that are due to changes in concentrations of biochemically relevant compounds in tissue is important in many clinical settings. One problem with such measurements is that the pathlength traveled by the collected light through the tissue depends on the scattering properties of the tissue. It is demonstrated, using both Monte Carlo simulations and experimental measurements, that for an appropriate separation between light-delivery and light-collection fibers, the pathlength of the collected photons is insensitive to scattering parameters for the range of parameters typically found in tissue. This is important for developing rapid, noninvasive, inexpensive, and accurate methods for measuring absorption changes in tissue.

Optical coherence tomography angiography-based capillary velocimetry

NASA Astrophysics Data System (ADS)

Wang, Ruikang K.; Zhang, Qinqin; Li, Yuandong; Song, Shaozhen

2017-06-01

Challenge persists in the field of optical coherence tomography (OCT) when it is required to quantify capillary blood flow within tissue beds in vivo. We propose a useful approach to statistically estimate the mean capillary flow velocity using a model-based statistical method of eigendecomposition (ED) analysis of the complex OCT signals obtained with the OCT angiography (OCTA) scanning protocol. ED-based analysis is achieved by the covariance matrix of the ensemble complex OCT signals, upon which the eigenvalues and eigenvectors that represent the subsets of the signal makeup are calculated. From this analysis, the signals due to moving particles can be isolated by employing an adaptive regression filter to remove the eigencomponents that represent static tissue signals. The mean frequency (MF) of moving particles can be estimated by the first lag-one autocorrelation of the corresponding eigenvectors. Three important parameters are introduced, including the blood flow signal power representing the presence of blood flow (i.e., OCTA signals), the MF indicating the mean velocity of blood flow, and the frequency bandwidth describing the temporal flow heterogeneity within a scanned tissue volume. The proposed approach is tested using scattering phantoms, in which microfluidic channels are used to simulate the functional capillary vessels that are perfused with the scattering intralipid solution. The results indicate a linear relationship between the MF and mean flow velocity. In vivo animal experiments are also conducted by imaging mouse brain with distal middle cerebral artery ligation to test the capability of the method to image the changes in capillary flows in response to an ischemic insult, demonstrating the practical usefulness of the proposed method for providing important quantifiable information about capillary tissue beds in the investigations of neurological conditions in vivo.

Correlation of breast tissue histology and optical signatures to improve margin assessment techniques

NASA Astrophysics Data System (ADS)

Kennedy, Stephanie; Caldwell, Matthew; Bydlon, Torre; Mulvey, Christine; Mueller, Jenna; Wilke, Lee; Barry, William; Ramanujam, Nimmi; Geradts, Joseph

2016-06-01

Optical spectroscopy is sensitive to morphological composition and has potential applications in intraoperative margin assessment. Here, we evaluate ex vivo breast tissue and corresponding quantified hematoxylin & eosin images to correlate optical scattering signatures to tissue composition stratified by patient characteristics. Adipose sites (213) were characterized by their cell area and density. All other benign and malignant sites (181) were quantified using a grid method to determine composition. The relationships between mean reduced scattering coefficient (<μs‧>), and % adipose, % collagen, % glands, adipocyte cell area, and adipocyte density were investigated. These relationships were further stratified by age, menopausal status, body mass index (BMI), and breast density. We identified a positive correlation between <μs‧> and % collagen and a negative correlation between <μs‧> and age and BMI. Increased collagen corresponded to increased <μs‧> variability. In postmenopausal women, <μs‧> was similar regardless of fibroglandular content. Contributions from collagen and glands to <μs‧> were independent and equivalent in benign sites; glands showed a stronger positive correlation than collagen to <μs‧> in malignant sites. Our data suggest that scattering could differentiate highly scattering malignant from benign tissues in postmenopausal women. The relationship between scattering and tissue composition will support improved scattering models and technologies to enhance intraoperative optical margin assessment.

Three-Dimensional Model of the Scatterer Distribution in Cirrhotic Liver

NASA Astrophysics Data System (ADS)

Yamaguchi, Tadashi; Nakamura, Keigo; Hachiya, Hiroyuki

2003-05-01

Ultrasonic B-mode images are affected by changes in scatterer distribution. It is hard to estimate the relationship between the ultrasonic image and the tissue structure quantitatively because we cannot observe the continuous stages of liver cirrhosis tissue clinically, particularly the beginning stage. In this paper, we propose a three-dimensional modeling method of scatterer distribution for normal and cirrhotic livers to confirm the influence of the change in the form of scatterer distribution on echo information. The algorithm of the method includes parameters which determine the expansion of nodules and fibers. Using the B-mode images which are obtained from these scatterer distributions, we analyze the relationship between the changes in the form of biological tissue and the changes in the B-mode images during progressive liver cirrhosis.

Analytical close-to-source investigation for an isotropic point source in an unbounded, anisotropically scattering medium

NASA Astrophysics Data System (ADS)

Rinzema, Kees; ten Bosch, Jaap J.; Ferwerda, Hedzer A.; Hoenders, Bernhard J.

1995-01-01

The diffusion approximation, which is often used to describe the propagation of light in biological tissues, is only good at a sufficient distance from sources and boundaries. Light- tissue interaction is however most intense in the region close to the source. It would therefore be interesting to study this region more closely. Although scattering in biological tissues is predominantly forward peaked, explicit solutions to the transport equation have only been obtained in the case of isotropic scattering. Particularly, for the case of an isotropic point source in an unbounded, isotropically scattering medium the solution is well known. We show that this problem can also be solved analytically if the scattering is no longer isotropic, while everything else remains the same.

Horizontal shear wave scattering from a nonwelded interface observed by magnetic resonance elastography

NASA Astrophysics Data System (ADS)

Papazoglou, S.; Hamhaber, U.; Braun, J.; Sack, I.

2007-02-01

A method based on magnetic resonance elastography is presented that allows measuring the weldedness of interfaces between soft tissue layers. The technique exploits the dependence of shear wave scattering at elastic interfaces on the frequency of vibration. Experiments were performed on gel phantoms including differently welded interfaces. Plane wave excitation parallel to the planar interface with corresponding motion sensitization enabled the observation of only shear-horizontal (SH) wave scattering. Spatio-temporal filtering was applied to calculate scattering coefficients from the amplitudes of the incident, transmitted and reflected SH-waves in the vicinity of the interface. The results illustrate that acoustic wave scattering in soft tissues is largely dependent on the connectivity of interfaces, which is potentially interesting for imaging tissue mechanics in medicine and biology.

Analysis of dense-medium light scattering with applications to corneal tissue: experiments and Monte Carlo simulations.

PubMed

Kim, K B; Shanyfelt, L M; Hahn, D W

2006-01-01

Dense-medium scattering is explored in the context of providing a quantitative measurement of turbidity, with specific application to corneal haze. A multiple-wavelength scattering technique is proposed to make use of two-color scattering response ratios, thereby providing a means for data normalization. A combination of measurements and simulations are reported to assess this technique, including light-scattering experiments for a range of polystyrene suspensions. Monte Carlo (MC) simulations were performed using a multiple-scattering algorithm based on full Mie scattering theory. The simulations were in excellent agreement with the polystyrene suspension experiments, thereby validating the MC model. The MC model was then used to simulate multiwavelength scattering in a corneal tissue model. Overall, the proposed multiwavelength scattering technique appears to be a feasible approach to quantify dense-medium scattering such as the manifestation of corneal haze, although more complex modeling of keratocyte scattering, and animal studies, are necessary.

PET brain kinetics studies of 11C-ITMM and 11C-ITDM,radioprobes for metabotropic glutamate receptor type 1, in a nonhuman primate

PubMed Central

Yamasaki, Tomoteru; Maeda, Jun; Fujinaga, Masayuki; Nagai, Yuji; Hatori, Akiko; Yui, Joji; Xie, Lin; Nengaki, Nobuki; Zhang, Ming-Rong

2014-01-01

The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed 11C-labeled PET probes 11C-ITMM and 11C-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared 11C-ITMM and 11C-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with 11C-ITDM than with 11C-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VT) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cm-3 for 11C-ITMM and 3.6 mL∙cm-3 for 11C-ITDM. By contrast, the VT in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of 11C-ITMM and 11C-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that 11C-ITDM may be superior to 11C-ITMM as a PET probe for imaging of mGluR1, because regional VT values in PET with 11C-ITDM were higher than those of 11C-ITMM. Clinical studies of 11C-ITDM in humans will be necessary in the future. PMID:24795840

PET brain kinetics studies of (11)C-ITMM and (11)C-ITDM,radioprobes for metabotropic glutamate receptor type 1, in a nonhuman primate.

PubMed

Yamasaki, Tomoteru; Maeda, Jun; Fujinaga, Masayuki; Nagai, Yuji; Hatori, Akiko; Yui, Joji; Xie, Lin; Nengaki, Nobuki; Zhang, Ming-Rong

2014-01-01

The metabotropic glutamate receptor type 1 (mGluR1) is a novel target protein for the development of new drugs against central nervous system disorders. Recently, we have developed (11)C-labeled PET probes (11)C-ITMM and (11)C-ITDM, which demonstrate similar profiles, for imaging of mGluR1. In the present study, we compared (11)C-ITMM and (11)C-ITDM PET imaging and quantitative analysis in the monkey brain. Respective PET images showed similar distribution of uptake in the cerebellum, thalamus, and cingulate cortex. Slightly higher uptake was detected with (11)C-ITDM than with (11)C-ITMM. For the kinetic analysis using the two-tissue compartment model (2-TCM), the distribution volume (VT) in the cerebellum, an mGluR1-rich region in the brain, was 2.5 mL∙cm(-3) for (11)C-ITMM and 3.6 mL∙cm(-3) for (11)C-ITDM. By contrast, the VT in the pons, a region with negligible mGluR1 expression, was similarly low for both radiopharmaceuticals. Based on these results, we performed noninvasive PET quantitative analysis with general reference tissue models using the time-activity curve of the pons as a reference region. We confirmed the relationship and differences between the reference tissue models and 2-TCM using correlational scatter plots and Bland-Altman plots analyses. Although the scattergrams of both radiopharmaceuticals showed over- or underestimations of reference tissue model-based the binding potentials against 2-TCM, there were no significant differences between the two kinetic analysis models. In conclusion, we first demonstrated the potentials of (11)C-ITMM and (11)C-ITDM for noninvasive PET quantitative analysis using reference tissue models. In addition, our findings suggest that (11)C-ITDM may be superior to (11)C-ITMM as a PET probe for imaging of mGluR1, because regional VT values in PET with (11)C-ITDM were higher than those of (11)C-ITMM. Clinical studies of (11)C-ITDM in humans will be necessary in the future.

Mannitol Improves Brain Tissue Oxygenation in a Model of Diffuse Traumatic Brain Injury.

PubMed

Schilte, Clotilde; Bouzat, Pierre; Millet, Anne; Boucheix, Perrine; Pernet-Gallay, Karin; Lemasson, Benjamin; Barbier, Emmanuel L; Payen, Jean-François

2015-10-01

Based on evidence supporting a potential relation between posttraumatic brain hypoxia and microcirculatory derangements with cell edema, we investigated the effects of the antiedematous agent mannitol on brain tissue oxygenation in a model of diffuse traumatic brain injury. Experimental study. Neurosciences and physiology laboratories. Adult male Wistar rats. Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were IV administered with either a saline solution (traumatic brain injury-saline group) or 20% mannitol (1 g/kg) (traumatic brain injury-mannitol group). Sham-saline and sham-mannitol groups received no insult. Two series of experiments were conducted 2 hours after traumatic brain injury (or equivalent) to investigate 1) the effect of mannitol on brain edema and oxygenation, using a multiparametric magnetic resonance-based approach (n = 10 rats per group) to measure the apparent diffusion coefficient, tissue oxygen saturation, mean transit time, and blood volume fraction in the cortex and caudoputamen; 2) the effect of mannitol on brain tissue PO2 and on venous oxygen saturation of the superior sagittal sinus (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 per group, taken from the first experiment). Compared with the sham-saline group, the traumatic brain injury-saline group had significantly lower tissue oxygen saturation, brain tissue PO2, and venous oxygen saturation of the superior sagittal sinus values concomitant with diffuse brain edema. These effects were associated with microcirculatory collapse due to astrocyte swelling. Treatment with mannitol after traumatic brain injury reversed all these effects. In the absence of traumatic brain injury, mannitol had no effect on brain oxygenation. Mean transit time and blood volume fraction were comparable between the four groups of rats. The development of posttraumatic brain edema can limit the oxygen utilization by brain tissue without evidence of brain ischemia. Our findings indicate that an antiedematous agent such as mannitol can improve brain tissue oxygenation, possibly by limiting astrocyte swelling and restoring capillary perfusion.

Method for accurate quantitation of background tissue optical properties in the presence of emission from a strong fluorescence marker

NASA Astrophysics Data System (ADS)

Bravo, Jaime; Davis, Scott C.; Roberts, David W.; Paulsen, Keith D.; Kanick, Stephen C.

2015-03-01

Quantification of targeted fluorescence markers during neurosurgery has the potential to improve and standardize surgical distinction between normal and cancerous tissues. However, quantitative analysis of marker fluorescence is complicated by tissue background absorption and scattering properties. Correction algorithms that transform raw fluorescence intensity into quantitative units, independent of absorption and scattering, require a paired measurement of localized white light reflectance to provide estimates of the optical properties. This study focuses on the unique problem of developing a spectral analysis algorithm to extract tissue absorption and scattering properties from white light spectra that contain contributions from both elastically scattered photons and fluorescence emission from a strong fluorophore (i.e. fluorescein). A fiber-optic reflectance device was used to perform measurements in a small set of optical phantoms, constructed with Intralipid (1% lipid), whole blood (1% volume fraction) and fluorescein (0.16-10 μg/mL). Results show that the novel spectral analysis algorithm yields accurate estimates of tissue parameters independent of fluorescein concentration, with relative errors of blood volume fraction, blood oxygenation fraction (BOF), and the reduced scattering coefficient (at 521 nm) of <7%, <1%, and <22%, respectively. These data represent a first step towards quantification of fluorescein in tissue in vivo.

Quantitative assessment of submicron scale anisotropy in tissue multifractality by scattering Mueller matrix in the framework of Born approximation

NASA Astrophysics Data System (ADS)

Das, Nandan Kumar; Dey, Rajib; Chakraborty, Semanti; Panigrahi, Prasanta K.; Meglinski, Igor; Ghosh, Nirmalya

2018-04-01

A number of tissue-like disordered media exhibit local anisotropy of scattering in the scaling behavior. Scaling behavior contains wealth of fractal or multifractal properties. We demonstrate that the spatial dielectric fluctuations in a sample of biological tissue exhibit multifractal anisotropy. Multifractal anisotropy encoded in the wavelength variation of the light scattering Mueller matrix and manifesting as an intriguing spectral diattenuation effect. We developed an inverse method for the quantitative assessment of the multifractal anisotropy. The method is based on the processing of relevant Mueller matrix elements in Fourier domain by using Born approximation, followed by the multifractal analysis. The approach promises for probing subtle micro-structural changes in biological tissues associated with the cancer and precancer, as well as for non-destructive characterization of a wide range of scattering materials.

Correction method for influence of tissue scattering for sidestream dark-field oximetry using multicolor LEDs

NASA Astrophysics Data System (ADS)

Kurata, Tomohiro; Oda, Shigeto; Kawahira, Hiroshi; Haneishi, Hideaki

2016-12-01

We have previously proposed an estimation method of intravascular oxygen saturation (SO_2) from the images obtained by sidestream dark-field (SDF) imaging (we call it SDF oximetry) and we investigated its fundamental characteristics by Monte Carlo simulation. In this paper, we propose a correction method for scattering by the tissue and performed experiments with turbid phantoms as well as Monte Carlo simulation experiments to investigate the influence of the tissue scattering in the SDF imaging. In the estimation method, we used modified extinction coefficients of hemoglobin called average extinction coefficients (AECs) to correct the influence from the bandwidth of the illumination sources, the imaging camera characteristics, and the tissue scattering. We estimate the scattering coefficient of the tissue from the maximum slope of pixel value profile along a line perpendicular to the blood vessel running direction in an SDF image and correct AECs using the scattering coefficient. To evaluate the proposed method, we developed a trial SDF probe to obtain three-band images by switching multicolor light-emitting diodes and obtained the image of turbid phantoms comprised of agar powder, fat emulsion, and bovine blood-filled glass tubes. As a result, we found that the increase of scattering by the phantom body brought about the decrease of the AECs. The experimental results showed that the use of suitable values for AECs led to more accurate SO_2 estimation. We also confirmed the validity of the proposed correction method to improve the accuracy of the SO_2 estimation.

Brain metastasis detection by resonant Raman optical biopsy method

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Cheng, Gangge; Zhou, Lixin; Zhang, Chunyuan; Pu, Yang; Li, Zhongwu; Liu, Yulong; Li, Qingbo; Wang, Wei; Alfano, Robert R.

2014-03-01

Resonant Raman (RR) spectroscopy provides an effective way to enhance Raman signal from particular bonds associated with key molecules due to changes on a molecular level. In this study, RR is used for detection of human brain metastases of five kinds of primary organs of lung, breast, kidney, rectal and orbital in ex-vivo. The RR spectra of brain metastases cancerous tissues were measured and compared with those of normal brain tissues and the corresponding primary cancer tissues. The differences of five types of brain metastases tissues in key bio-components of carotene, tryptophan, lactate, alanine and methyl/methylene group were investigated. The SVM-KNN classifier was used to categorize a set of RR spectra data of brain metastasis of lung cancerous tissues from normal brain tissue, yielding diagnostic sensitivity and specificity at 100% and 75%, respectively. The RR spectroscopy may provide new moleculebased optical probe tools for diagnosis and classification of brain metastatic of cancers.

Nanoencapsulation of the sasanquasaponin from Camellia oleifera, its photo responsiveness and neuroprotective effects.

PubMed

Ye, Yong; Xing, Haiting; Li, Yue

2014-01-01

Sasanquasaponin, a bioactive compound isolated from seeds of Camellia oleifera, shows central effects in our previous research. In order to investigate its neuroprotective effects, a new kind of nanocapsule with photo responsiveness was designed to deliver sasanquasaponin into the brain and adjusted by red light. The nanocapsule was prepared using sasanquasaponin emulsified with soybean lecithin and cholesterol solution. The natural phaeophorbide from silkworm excrement as a photosensitizer was added in the lipid phase to make the nanocapsules photo responsive. The physicochemical properties of encapsulation efficiency, size distribution, morphology and stability were measured using high-performance liquid chromatography, particle size analyzer, transmission electron microscope, differential scanning calorimetry and thermogravimetry. Photo responsiveness was determined by the sasanquasaponin release in pH 7.5 phosphate buffer under the laser at 670 nm. The neuroprotective effects were evaluated by the expression of tyrosine hydroxylase (TH), decrease of inflammatory cytokines TNF-α and IL-1β in the brain, and amelioration of kainic acid-induced behavioral disorder in mice. The nanocapsules had higher encapsulation efficiency and stability when the phaeophorbide content was 2% of lecithin weight. The average size was 172.2 nm, distributed in the range of 142-220 nm. The phaeophorbide was scattered sufficiently in the outer lecithin layer of the nanocapsules and increased the drug release after irradiation. TH expression in brain tissues and locomotive activities in mice were reduced by kainic acid, but could be improved by the sasanquasaponin nanocapsules after tail vein injection with 15 minutes of irradiation at the nasal cavity. The sasanquasaponin took effect through inflammatory alleviation in central tissues. The sasanquasaponin nanocapsules with phaeophorbide have photo responsiveness and neuroprotective effects under the irradiation of red light. This preparation presents a new approach to brain neuroprotection, and has potential for clinical application.

Development of integrated semiconductor optical sensors for functional brain imaging

NASA Astrophysics Data System (ADS)

Lee, Thomas T.

Optical imaging of neural activity is a widely accepted technique for imaging brain function in the field of neuroscience research, and has been used to study the cerebral cortex in vivo for over two decades. Maps of brain activity are obtained by monitoring intensity changes in back-scattered light, called Intrinsic Optical Signals (IOS), that correspond to fluctuations in blood oxygenation and volume associated with neural activity. Current imaging systems typically employ bench-top equipment including lamps and CCD cameras to study animals using visible light. Such systems require the use of anesthetized or immobilized subjects with craniotomies, which imposes limitations on the behavioral range and duration of studies. The ultimate goal of this work is to overcome these limitations by developing a single-chip semiconductor sensor using arrays of sources and detectors operating at near-infrared (NIR) wavelengths. A single-chip implementation, combined with wireless telemetry, will eliminate the need for immobilization or anesthesia of subjects and allow in vivo studies of free behavior. NIR light offers additional advantages because it experiences less absorption in animal tissue than visible light, which allows for imaging through superficial tissues. This, in turn, reduces or eliminates the need for traumatic surgery and enables long-term brain-mapping studies in freely-behaving animals. This dissertation concentrates on key engineering challenges of implementing the sensor. This work shows the feasibility of using a GaAs-based array of vertical-cavity surface emitting lasers (VCSELs) and PIN photodiodes for IOS imaging. I begin with in-vivo studies of IOS imaging through the skull in mice, and use these results along with computer simulations to establish minimum performance requirements for light sources and detectors. I also evaluate the performance of a current commercial VCSEL for IOS imaging, and conclude with a proposed prototype sensor.

Spatial cluster analysis of nanoscopically mapped serotonin receptors for classification of fixed brain tissue

NASA Astrophysics Data System (ADS)

Sams, Michael; Silye, Rene; Göhring, Janett; Muresan, Leila; Schilcher, Kurt; Jacak, Jaroslaw

2014-01-01

We present a cluster spatial analysis method using nanoscopic dSTORM images to determine changes in protein cluster distributions within brain tissue. Such methods are suitable to investigate human brain tissue and will help to achieve a deeper understanding of brain disease along with aiding drug development. Human brain tissue samples are usually treated postmortem via standard fixation protocols, which are established in clinical laboratories. Therefore, our localization microscopy-based method was adapted to characterize protein density and protein cluster localization in samples fixed using different protocols followed by common fluorescent immunohistochemistry techniques. The localization microscopy allows nanoscopic mapping of serotonin 5-HT1A receptor groups within a two-dimensional image of a brain tissue slice. These nanoscopically mapped proteins can be confined to clusters by applying the proposed statistical spatial analysis. Selected features of such clusters were subsequently used to characterize and classify the tissue. Samples were obtained from different types of patients, fixed with different preparation methods, and finally stored in a human tissue bank. To verify the proposed method, samples of a cryopreserved healthy brain have been compared with epitope-retrieved and paraffin-fixed tissues. Furthermore, samples of healthy brain tissues were compared with data obtained from patients suffering from mental illnesses (e.g., major depressive disorder). Our work demonstrates the applicability of localization microscopy and image analysis methods for comparison and classification of human brain tissues at a nanoscopic level. Furthermore, the presented workflow marks a unique technological advance in the characterization of protein distributions in brain tissue sections.

Psychiatric Brain Banking: Three Perspectives on Current Trends and Future Directions

PubMed Central

Deep-Soboslay, Amy; Benes, Francine M.; Haroutunian, Vahram; Ellis, Justin K.; Kleinman, Joel E.; Hyde, Thomas M.

2011-01-01

Introduction The study of postmortem human brain tissue is central to the advancement of the neurobiological studies of psychiatric illness, particularly for the study of brain-specific isoforms and molecules. Methods The state-of-the-art methods and recommendations for maintaining a successful brain bank for psychiatric disorders are discussed, using the convergence of viewpoints from three brain collections, the National Institute of Mental Health Brain Collection (NIMH), the Harvard Brain Tissue Resource Center (HBTRC), and the Mt. Sinai School of Medicine Brain Bank (MSSM-BB), with diverse research interests and divergent approaches to tissue acquisition. Results While the NIMH obtains donations from medical examiners for its collection, and places particular emphasis on clinical diagnosis, toxicology, and building lifespan control cohorts, the HBTRC is uniquely designed as a repository whose sole purpose is to collect large-volume, high quality brain tissue from community-based donors based on relationships across an expansive nationwide network, and places emphasis on the accessibility of its bank in disseminating tissue and related data to research groups worldwide. The MSSM-BB collection has shown that, with dedication, prospective recruitment is a successful approach to tissue donation, and places particular emphasis on rigorous clinical diagnosis through antemortem contact with donors. The MSSM-BB places great importance on stereological tissue sampling methods for neuroanatomical studies, and frozen tissue sampling approaches that enable multiple assessments (RNA, DNA, protein, enzyme activity, binding, etc.) of the same tissue block. Promising scientific approaches for elucidating the molecular and cellular pathways in brain that may contribute to schizophrenia and/or bipolar disorder, such as cell culture techniques and microarray-based gene expression and genotyping studies are briefly discussed. Conclusions Despite unique perspectives from three established brain collections, there is a consensus that (1) diverse strategies for tissue acquisition, (2) rigor in tissue and diagnostic characterization, (3) the importance of sample accessibility, and (4) continual application of innovative scientific approaches to the study of brain tissue are all integral to the success and future of psychiatric brain banking. The future of neuropsychiatric research depends upon in the availability of high quality brain specimens from large numbers of subjects, including non-psychiatric controls. PMID:20673875

Effect of luminescence transport through adipose tissue on measurement of tissue temperature by using ZnCdS nanothermometers

NASA Astrophysics Data System (ADS)

Volkova, Elena K.; Yanina, Irina Yu.; Sagaydachnaya, Elena; Konyukhova, Julia G.; Kochubey, Vyacheslav I.; Tuchin, Valery V.

2018-02-01

The spectra of luminescence of ZnCdS nanoparticles (ZnCdS NPs) were measured and analyzed in a wide temperature range: from room to human body and further to a hyperthermic temperature resulting in tissue morphology change. The results show that the signal of luminescence of ZnCdS NPs placed within the tissue is reasonably good sensitive to temperature change and accompanied by phase transitions of lipid structures of adipose tissue. It is shown that the presence of a phase transition in adipose tissue upon its heating (polymorphic transformations of lipids) leads to a nonmonotonic temperature dependence of the intensity of luminescence for the nanoparticles introduced into adipose tissue. This is due to a change in the light scattering by the tissue. The light scattering of adipose tissue greatly distorts the results of temperature measurements. The application of these nanoparticles is possible for temperature measurements in very thin or weakly scattering samples.

Depth discrimination in acousto-optic cerebral blood flow measurement simulation

NASA Astrophysics Data System (ADS)

Tsalach, A.; Schiffer, Z.; Ratner, E.; Breskin, I.; Zeitak, R.; Shechter, R.; Balberg, M.

2016-03-01

Monitoring cerebral blood flow (CBF) is crucial, as inadequate perfusion, even for relatively short periods of time, may lead to brain damage or even death. Thus, significant research efforts are directed at developing reliable monitoring tools that will enable continuous, bed side, simple and cost-effective monitoring of CBF. All existing non invasive bed side monitoring methods, which are mostly NIRS based, such as Laser Doppler or DCS, tend to underestimate CBF in adults, due to the indefinite effect of extra-cerebral tissues on the obtained signal. If those are to find place in day to day clinical practice, the contribution of extra-cerebral tissues must be eliminated and data from the depth (brain) should be extracted and discriminated. Recently, a novel technique, based on ultrasound modulation of light was developed for non-invasive, continuous CBF monitoring (termed ultrasound-tagged light (UTL or UT-NIRS)), and shown to correlate with readings of 133Xe SPECT and laser Doppler. We have assembled a comprehensive computerized simulation, modeling this acousto-optic technique in a highly scattering media. Using the combination of light and ultrasound, we show how depth information may be extracted, thus distinguishing between flow patterns taking place at different depths. Our algorithm, based on the analysis of light modulated by ultrasound, is presented and examined in a computerized simulation. Distinct depth discrimination ability is presented, suggesting that using such method one can effectively nullify the extra-cerebral tissues influence on the obtained signals, and specifically extract cerebral flow data.

A breast-specific, negligible-dose scatter correction technique for dedicated cone-beam breast CT: a physics-based approach to improve Hounsfield Unit accuracy

NASA Astrophysics Data System (ADS)

Yang, Kai; Burkett, George, Jr.; Boone, John M.

2014-11-01

The purpose of this research was to develop a method to correct the cupping artifact caused from x-ray scattering and to achieve consistent Hounsfield Unit (HU) values of breast tissues for a dedicated breast CT (bCT) system. The use of a beam passing array (BPA) composed of parallel-holes has been previously proposed for scatter correction in various imaging applications. In this study, we first verified the efficacy and accuracy using BPA to measure the scatter signal on a cone-beam bCT system. A systematic scatter correction approach was then developed by modeling the scatter-to-primary ratio (SPR) in projection images acquired with and without BPA. To quantitatively evaluate the improved accuracy of HU values, different breast tissue-equivalent phantoms were scanned and radially averaged HU profiles through reconstructed planes were evaluated. The dependency of the correction method on object size and number of projections was studied. A simplified application of the proposed method on five clinical patient scans was performed to demonstrate efficacy. For the typical 10-18 cm breast diameters seen in the bCT application, the proposed method can effectively correct for the cupping artifact and reduce the variation of HU values of breast equivalent material from 150 to 40 HU. The measured HU values of 100% glandular tissue, 50/50 glandular/adipose tissue, and 100% adipose tissue were approximately 46, -35, and -94, respectively. It was found that only six BPA projections were necessary to accurately implement this method, and the additional dose requirement is less than 1% of the exam dose. The proposed method can effectively correct for the cupping artifact caused from x-ray scattering and retain consistent HU values of breast tissues.

Focusing light inside dynamic scattering media with millisecond digital optical phase conjugation

PubMed Central

Liu, Yan; Ma, Cheng; Shen, Yuecheng; Shi, Junhui; Wang, Lihong V.

2017-01-01

Wavefront shaping based on digital optical phase conjugation (DOPC) focuses light through or inside scattering media, but the low speed of DOPC prevents it from being applied to thick, living biological tissue. Although a fast DOPC approach was recently developed, the reported single-shot wavefront measurement method does not work when the goal is to focus light inside, instead of through, highly scattering media. Here, using a ferroelectric liquid crystal based spatial light modulator, we develop a simpler but faster DOPC system that focuses light not only through, but also inside scattering media. By controlling 2.6 × 105 optical degrees of freedom, our system focused light through 3 mm thick moving chicken tissue, with a system latency of 3.0 ms. Using ultrasound-guided DOPC, along with a binary wavefront measurement method, our system focused light inside a scattering medium comprising moving tissue with a latency of 6.0 ms, which is one to two orders of magnitude shorter than those of previous digital wavefront shaping systems. Since the demonstrated speed approaches tissue decorrelation rates, this work is an important step toward in vivo deep-tissue non-invasive optical imaging, manipulation, and therapy. PMID:28815194

Mapping local orientation of aligned fibrous scatterers for cancerous tissues using backscattering Mueller matrix imaging

NASA Astrophysics Data System (ADS)

He, Honghui; Sun, Minghao; Zeng, Nan; Du, E.; Liu, Shaoxiong; Guo, Yihong; Wu, Jian; He, Yonghong; Ma, Hui

2014-10-01

Polarization measurements are sensitive to the microstructure of tissues and can be used to detect pathological changes. Many tissues contain anisotropic fibrous structures. We obtain the local orientation of aligned fibrous scatterers using different groups of the backscattering Mueller matrix elements. Experiments on concentrically well-aligned silk fibers and unstained human papillary thyroid carcinoma tissues show that the m22, m33, m23, and m32 elements have better contrast but higher degeneracy for the extraction of orientation angles. The m12 and m13 elements show lower contrast, but allow us to determine the orientation angle for the fibrous scatterers along all directions. Moreover, Monte Carlo simulations based on the sphere-cylinder scattering model indicate that the oblique incidence of the illumination beam introduces some errors in the orientation angles obtained by both methods. Mapping the local orientation of anisotropic tissues may not only provide information on pathological changes, but can also give new leads to reduce the orientation dependence of polarization measurements.

Preclinical evaluation of spatial frequency domain-enabled wide-field quantitative imaging for enhanced glioma resection

NASA Astrophysics Data System (ADS)

Sibai, Mira; Fisher, Carl; Veilleux, Israel; Elliott, Jonathan T.; Leblond, Frederic; Roberts, David W.; Wilson, Brian C.

2017-07-01

5-Aminolevelunic acid-induced protoporphyrin IX (PpIX) fluorescence-guided resection (FGR) enables maximum safe resection of glioma by providing real-time tumor contrast. However, the subjective visual assessment and the variable intrinsic optical attenuation of tissue limit this technique to reliably delineating only high-grade tumors that display strong fluorescence. We have previously shown, using a fiber-optic probe, that quantitative assessment using noninvasive point spectroscopic measurements of the absolute PpIX concentration in tissue further improves the accuracy of FGR, extending it to surgically curable low-grade glioma. More recently, we have shown that implementing spatial frequency domain imaging with a fluorescent-light transport model enables recovery of two-dimensional images of [PpIX], alleviating the need for time-consuming point sampling of the brain surface. We present first results of this technique modified for in vivo imaging on an RG2 rat brain tumor model. Despite the moderate errors in retrieving the absorption and reduced scattering coefficients in the subdiffusive regime of 14% and 19%, respectively, the recovered [PpIX] maps agree within 10% of the point [PpIX] values measured by the fiber-optic probe, validating its potential as an extension or an alternative to point sampling during glioma resection.

Photon migration in non-scattering tissue and the effects on image reconstruction

NASA Astrophysics Data System (ADS)

Dehghani, H.; Delpy, D. T.; Arridge, S. R.

1999-12-01

Photon propagation in tissue can be calculated using the relationship described by the transport equation. For scattering tissue this relationship is often simplified and expressed in terms of the diffusion approximation. This approximation, however, is not valid for non-scattering regions, for example cerebrospinal fluid (CSF) below the skull. This study looks at the effects of a thin clear layer in a simple model representing the head and examines its effect on image reconstruction. Specifically, boundary photon intensities (total number of photons exiting at a point on the boundary due to a source input at another point on the boundary) are calculated using the transport equation and compared with data calculated using the diffusion approximation for both non-scattering and scattering regions. The effect of non-scattering regions on the calculated boundary photon intensities is presented together with the advantages and restrictions of the transport code used. Reconstructed images are then presented where the forward problem is solved using the transport equation for a simple two-dimensional system containing a non-scattering ring and the inverse problem is solved using the diffusion approximation to the transport equation.

Perspectives of multimode fibers and digital holography for optogenetics

NASA Astrophysics Data System (ADS)

Czarske, Jürgen W.; Haufe, Daniel; Koukourakis, Nektarios; Büttner, Lars

2016-04-01

Optogenetic approaches allow the activation or inhibition of genetically prescribed populations of neurons by light. In principle, optogenetics offers not only the ability to elucidate the functions of neural circuitry, but also new approaches to a treatment of neurodegenerative diseases and recovery of vision and auditory perception. Optogenetics already has revolutionized research in neuroscience. However, new methods for delivering light to three-dimensionally distributed structures e.g. in the brain are necessary. A major hurdle for focusing light through biological tissue is the occurring scattering and scrambling of the light. We demonstrate the correction of the scrambling in a multimode fiber by digital optical phase conjugation with a perspective for optogenetics.

Ultra-fast 3D scanning and holographic illumination in non-linear microscopy using acousto-optic deflectors

NASA Astrophysics Data System (ADS)

Akemann, Walther; Ventalon, Cathie; Léger, Jean-François; Mathieu, Benjamin; Dieudonné, Stéphane; Blochet, Baptiste; Gigan, Sylvain; Bourdieu, Laurent

2017-04-01

Decoding of information in the brain requires the imaging of large neuronal networks using e.g. two-photon microscopy (TPM). Fast control of the focus in 3D can be achieved with phase shaping of the light beam using acoustooptic deflectors (AODs). However, beam shaping using AODs is not straightforward because of non-stationary of acousto-optic diffraction. Here, we demonstrated a new stable AOD-based phase modulator, which operates at a rate of up to about hundred kHz. It provides opportunity for 3D scanning in TPM with the possibility to correct aberrations independently for every focus position or to achieve refocusing of scattered photons in rapidly decorrelating tissues.

Autofluorescence detection and imaging of bladder cancer realized through a cystoscope

DOEpatents

Demos, Stavros G [Livermore, CA; deVere White, Ralph W [Sacramento, CA

2007-08-14

Near infrared imaging using elastic light scattering and tissue autofluorescence and utilizing interior examination techniques and equipment are explored for medical applications. The approach involves imaging using cross-polarized elastic light scattering and/or tissue autofluorescence in the Near Infra-Red (NIR) coupled with image processing and inter-image operations to differentiate human tissue components.

Frequency of brain tissue donation for research after suicide.

PubMed

Longaray, Vanessa K; Padoan, Carolina S; Goi, Pedro D; da Fonseca, Rodrigo C; Vieira, Daniel C; Oliveira, Francine H de; Kapczinski, Flávio; Magalhães, Pedro V

2017-01-01

To describe the frequency of brain tissue donation for research purposes by families of individuals that committed suicide. All requests for brain tissue donation to a brain biorepository made to the families of individuals aged 18-60 years who had committed suicide between March 2014 and February 2016 were included. Cases presenting with brain damage due to acute trauma were excluded. Fifty-six cases of suicide were reported. Of these, 24 fulfilled the exclusion criteria, and 11 others were excluded because no next of kin was found to provide informed consent. Of the 21 remaining cases, brain tissue donation was authorized in nine (tissue fragments in seven and the entire organ in two). Donation of brain tissue from suicide cases for research purposes is feasible. The acceptance rate of 42.8% in our sample is in accordance with international data on such donations, and similar to rates reported for neurodegenerative diseases.

Metastasis Infiltration: An Investigation of the Postoperative Brain-Tumor Interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raore, Bethwel; Schniederjan, Matthew; Prabhu, Roshan

Purpose: This study aims to evaluate brain infiltration of metastatic tumor cells past the main tumor resection margin to assess the biological basis for the use of stereotactic radiosurgery treatment of the tumor resection cavity and visualized resection edge or clinical target volume. Methods and Materials: Resection margin tissue was obtained after gross total resection of a small group of metastatic lesions from a variety of primary sources. The tissue at the border of the tumor and brain tissue was carefully oriented and processed to evaluate the presence of tumor cells within brain tissue and their distance from the resectionmore » margin. Results: Microscopic assessment of the radially oriented tissue samples showed no tumor cells infiltrating the surrounding brain tissue. Among the positive findings were reactive astrocytosis observed on the brain tissue immediately adjacent to the tumor resection bed margin. Conclusions: The lack of evidence of metastatic tumor cell infiltration into surrounding brain suggests the need to target only a narrow depth of the resection cavity margin to minimize normal tissue injury and prevent treatment size-dependent stereotactic radiosurgery complications.« less

NMR imaging of cell phone radiation absorption in brain tissue

PubMed Central

Gultekin, David H.; Moeller, Lothar

2013-01-01

A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry. PMID:23248293

NMR imaging of cell phone radiation absorption in brain tissue.

PubMed

Gultekin, David H; Moeller, Lothar

2013-01-02

A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry.

Probing multi-scale self-similarity of tissue structures using light scattering spectroscopy: prospects in pre-cancer detection

NASA Astrophysics Data System (ADS)

Chatterjee, Subhasri; Das, Nandan K.; Kumar, Satish; Mohapatra, Sonali; Pradhan, Asima; Panigrahi, Prasanta K.; Ghosh, Nirmalya

2013-02-01

Multi-resolution analysis on the spatial refractive index inhomogeneities in the connective tissue regions of human cervix reveals clear signature of multifractality. We have thus developed an inverse analysis strategy for extraction and quantification of the multifractality of spatial refractive index fluctuations from the recorded light scattering signal. The method is based on Fourier domain pre-processing of light scattering data using Born approximation, and its subsequent analysis through Multifractal Detrended Fluctuation Analysis model. The method has been validated on several mono- and multi-fractal scattering objects whose self-similar properties are user controlled and known a-priori. Following successful validation, this approach has initially been explored for differentiating between different grades of precancerous human cervical tissues.

Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

PubMed

Stewart, Daniel C; Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S

2017-01-01

While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

Monitoring the process of tissue healing of rat skin in vivo after laser irradiation based on optical coherence tomography

NASA Astrophysics Data System (ADS)

He, Youwu; Wu, Shulian; Li, Zhifang; Cai, Shoudong; Li, Hui

2010-11-01

It is imperative to evaluate the tissue wound healing response after laser irradiation so as to develop effective devices for this clinical indication, and evaluate the thermal damage degree to take appropriate treatment. In our research, we prepare 6 white rat (approximately 2 months old, weight :28+/-2g). Each rat was injected intraperitoneally a single dose of 2% pentobarbital sodium. After the rat was anesthetized, the two side of the rats' back were denuded and antisepsised a standardized. An Er:YAG laser (2940nm, 2.5J/cm2, single spot, 4 times) was irradiated on rat skin in vivo, and the skin which before irradiated and the process of renovating scathe that irradiated after Er:YAG laser were observed by an Optical coherence tomography (OCT). The tissue recovery is about a twelve -day period. The results indicate that the scattering coefficient of post- tissue has changed distinctly. The and flexibility fiber is the chief component of rat dermis and the collagen is the main scattering material. The normal tissue has a large scattering coefficient, after laser irradiated, the collagen became concreting and putrescence and caused the structure change. It became more uniform density distribution, which results in a reduced scattering coefficient. In a word, OCT can noninvasively monitor changes in collagen structure and the recover process in thermal damage through monitor the tissue scattering coefficient.

Non-Scanning Fiber-Optic Near-Infrared Beam Led to Two-Photon Optogenetic Stimulation In-Vivo

PubMed Central

Shivalingaiah, Shivaranjani; Dennis, Torry S.; Morris-Bobzean, Samara A.; Li, Ting; Perrotti, Linda I.; Mohanty, Samarendra K.

2014-01-01

Stimulation of specific neurons expressing opsins in a targeted region to manipulate brain function has proved to be a powerful tool in neuroscience. However, the use of visible light for optogenetic stimulation is invasive due to low penetration depth and tissue damage owing to larger absorption and scattering. Here, we report, for the first time, in-depth non-scanning fiber-optic two-photon optogenetic stimulation (FO-TPOS) of neurons in-vivo in transgenic mouse models. In order to optimize the deep-brain stimulation strategy, we characterized two-photon activation efficacy at different near-infrared laser parameters. The significantly-enhanced in-depth stimulation efficiency of FO-TPOS as compared to conventional single-photon beam was demonstrated both by experiments and Monte Carlo simulation. The non-scanning FO-TPOS technology will lead to better understanding of the in-vivo neural circuitry because this technology permits more precise and less invasive anatomical delivery of stimulation. PMID:25383687

Hybrid system for in vivo real-time planar fluorescence and volumetric optoacoustic imaging

NASA Astrophysics Data System (ADS)

Chen, Zhenyue; Deán-Ben, Xosé Luís.; Gottschalk, Sven; Razansky, Daniel

2018-02-01

Fluorescence imaging is widely employed in all fields of cell and molecular biology due to its high sensitivity, high contrast and ease of implementation. However, the low spatial resolution and lack of depth information, especially in strongly-scattering samples, restrict its applicability for deep-tissue imaging applications. On the other hand, optoacoustic imaging is known to deliver a unique set of capabilities such as high spatial and temporal resolution in three dimensions, deep penetration and spectrally-enriched imaging contrast. Since fluorescent substances can generate contrast in both modalities, simultaneous fluorescence and optoacoustic readings can provide new capabilities for functional and molecular imaging of living organisms. Optoacoustic images can further serve as valuable anatomical references based on endogenous hemoglobin contrast. Herein, we propose a hybrid system for in vivo real-time planar fluorescence and volumetric optoacoustic tomography, both operating in reflection mode, which synergistically combines the advantages of stand-alone systems. Validation of the spatial resolution and sensitivity of the system were first carried out in tissue mimicking phantoms while in vivo imaging was further demonstrated by tracking perfusion of an optical contrast agent in a mouse brain in the hybrid imaging mode. Experimental results show that the proposed system effectively exploits the contrast mechanisms of both imaging modalities, making it especially useful for accurate monitoring of fluorescence-based signal dynamics in highly scattering samples.

Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice

PubMed Central

Imitola, Jaime; Côté, Daniel; Rasmussen, Stine; Xie, X. Sunney; Liu, Yingru; Chitnis, Tanuja; Sidman, Richard L.; Lin, Charles. P.; Khoury, Samia J.

2011-01-01

Myelin loss and axonal degeneration predominate in many neurological disorders; however, methods to visualize them simultaneously in live tissue are unavailable. We describe a new imaging strategy combining video rate reflectance and fluorescence confocal imaging with coherent anti-Stokes Raman scattering (CARS) microscopy tuned to CH2 vibration of myelin lipids, applied in live tissue of animals with chronic experimental autoimmune encephalomyelitis (EAE). Our method allows monitoring over time of demyelination and neurodegeneration in brain slices with high spatial resolution and signal-to-noise ratio. Local areas of severe loss of lipid signal indicative of demyelination and loss of the reflectance signal from axons were seen in the corpus callosum and spinal cord of EAE animals. Even in myelinated areas of EAE mice, the intensity of myelin lipid signals is significantly reduced. Using heterozygous knock-in mice in which green fluorescent protein replaces the CX3CR1 coding sequence that labels central nervous system microglia, we find areas of activated microglia colocalized with areas of altered reflectance and CARS signals reflecting axonal injury and demyelination. Our data demonstrate the use of multimodal CARS microscopy for characterization of demyelinating and neurodegenerative pathology in a mouse model of multiple sclerosis, and further confirm the critical role of microglia in chronic inflammatory neurodegeneration. PMID:21361672

Laser Speckle Imaging of Blood Flow Beneath Static Scattering Media

NASA Astrophysics Data System (ADS)

Regan, Caitlin Anderson

Laser speckle imaging (LSI) is a wide-field optical imaging technique that provides information about the movement of scattering particles in biological samples. LSI is used to create maps of relative blood flow and perfusion in samples such as the skin, brain, teeth, gingiva, and other biological tissues. The presence of static, or non-moving, optical scatterers affects the ability of LSI to provide true quantitative and spatially resolved measurements of blood flow. With in vitro experiments using tissue-simulating phantoms, we determined that temporal analysis of raw speckle image sequences improved the quantitative accuracy of LSI to measure flow beneath a static scattering layer. We then applied the temporal algorithm to assess the potential of LSI to monitor oral health. We designed and tested two generations of miniature LSI devices to measure flow in the pulpal chamber of teeth and in the gingiva. Our preliminary clinical pilot data indicated that speckle contrast may correlate with gingival health. To improve visualization of subsurface blood vessels, we developed a technique called photothermal LSI. We applied a short pulse of laser energy to selectively perturb the motion of red blood cells, increasing the signal from vasculature relative to the surroundings. To study the spectral and depth dependence of laser speckle contrast, we developed a Monte Carlo model of light and momentum transport to simulate speckle contrast. With an increase in the thickness of the overlying static-scattering layer, we observed a quadratic decrease in the quantity of dynamically scattered light collected by the detector. We next applied the model to study multi-exposure speckle imaging (MESI), a method that purportedly improves quantitative accuracy of subsurface blood flow measurements. We unexpectedly determined that MESI faced similar depth limitations as conventional LSI, findings that were supported by in vitro experimental data. Finally, we used the model to study the effects of epidermal melanin absorption on LSI, and demonstrated that speckle contrast is less sensitive to varying melanin content than reflectance. We then proposed a two-wavelength measurement protocol that may enable melanin-independent LSI measurements of blood flow in patients with varying skin types. In conclusion, through in vitro and in silico experiments, we were able to further the understanding of the depth dependent origins of laser speckle contrast as well as the inherent limitations of this technology.

Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography.

PubMed

Guertler, Charlotte A; Okamoto, Ruth J; Schmidt, John L; Badachhape, Andrew A; Johnson, Curtis L; Bayly, Philip V

2018-03-01

The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies. Copyright © 2018 Elsevier Ltd. All rights reserved.

In vitro 3D regeneration-like growth of human patient brain tissue.

PubMed

Tang-Schomer, M D; Wu, W B; Kaplan, D L; Bookland, M J

2018-05-01

In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 μm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models. Copyright © 2018 John Wiley & Sons, Ltd.

Scatter sensitive microscopic techniques to identify contrasting mucosal structures in ultrahigh-resolution optical coherence tomograms of mouse colon

NASA Astrophysics Data System (ADS)

Tumlinson, Alexandre R.; Hariri, Lida P.; Drexler, Wolfgang; Barton, Jennifer K.

2008-02-01

Optical coherence tomography, optical coherence microscopy, reflectance confocal microscopy, and darkfield microscopy all derive contrast from the intensity of endogenous tissue scatter. We have imaged excised mouse colon tissue with these complimentary technologies to make conclusions about structural origins of scatter in the mouse colonic mucosa observed with endoscopic OCT. We find hyperintense scattering both from the cytoplasm of epithelial cells and from the boundary between epithelia and the lamina propria. We find almost no scatter from the portion of epithelial cells containing the nucleus. These observations substantiate explanations for the appearance of colonic crypts and the luminal surface.

Mueller matrix approach for probing multifractality in the underlying anisotropic connective tissue

NASA Astrophysics Data System (ADS)

Das, Nandan Kumar; Dey, Rajib; Ghosh, Nirmalya

2016-09-01

Spatial variation of refractive index (RI) in connective tissues exhibits multifractality, which encodes useful morphological and ultrastructural information about the disease. We present a spectral Mueller matrix (MM)-based approach in combination with multifractal detrended fluctuation analysis (MFDFA) to exclusively pick out the signature of the underlying connective tissue multifractality through the superficial epithelium layer. The method is based on inverse analysis on selected spectral scattering MM elements encoding the birefringence information on the anisotropic connective tissue. The light scattering spectra corresponding to the birefringence carrying MM elements are then subjected to the Born approximation-based Fourier domain preprocessing to extract ultrastructural RI fluctuations of anisotropic tissue. The extracted RI fluctuations are subsequently analyzed via MFDFA to yield the multifractal tissue parameters. The approach was experimentally validated on a simple tissue model comprising of TiO2 as scatterers of the superficial isotropic layer and rat tail collagen as an underlying anisotropic layer. Finally, the method enabled probing of precancer-related subtle alterations in underlying connective tissue ultrastructural multifractality from intact tissues.

Electron density of Rhizophora spp. wood using Compton scattering technique at 15.77, 17.48 and 22.16 keV XRF energies

NASA Astrophysics Data System (ADS)

Shakhreet, B. Z.; Bauk, S.; Shukri, A.

2015-02-01

Compton (incoherently) scattered photons which are directly proportional to the electron density of the scatterer, have been employed in characterizing Rhizophora spp. as breast tissue equivalent. X-ray fluorescent scattered incoherently from Rhizophora spp. sample was measured using Si-PIN detector and three XRF energy values 15.77, 17.48 and 22.16 keV. This study is aimed at providing electron density information in support of the introduction of new tissue substitute materials for mammography phantoms.

Dependence of light scattering profile in tissue on blood vessel diameter and distribution: a computer simulation study.

PubMed

Duadi, Hamootal; Fixler, Dror; Popovtzer, Rachela

2013-11-01

Most methods for measuring light-tissue interactions focus on the volume reflectance while very few measure the transmission. We investigate both diffusion reflection and diffuse transmission at all exit angles to receive the full scattering profile. We also investigate the influence of blood vessel diameter on the scattering profile of a circular tissue. The photon propagation path at a wavelength of 850 nm is calculated from the absorption and scattering constants via Monte Carlo simulation. Several simulations are performed where a different vessel diameter and location were chosen but the blood volume was kept constant. The fraction of photons exiting the tissue at several central angles is presented for each vessel diameter. The main result is that there is a central angle that below which the photon transmission decreased for lower vessel diameters while above this angle the opposite occurred. We find this central angle to be 135 deg for a two-dimensional 10-mm diameter circular tissue cross-section containing blood vessels. These findings can be useful for monitoring blood perfusion and oxygen delivery in the ear lobe and pinched tissues. © 2013 Society of Photo-Optical Instrumentation Engineers (SPIE)

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats

PubMed Central

Pong, Alice C.; Jugé, Lauriane; Bilston, Lynne E.; Cheng, Shaokoon

2017-01-01

Introduction Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Methods Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Results Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls. Conclusions This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus. PMID:28837671

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

PubMed

Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

2017-01-01

Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls. This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

Coherent light depolarization by multiple scattering media and tissues: some fundamentals and applications

NASA Astrophysics Data System (ADS)

Zimnyakov, Dmitry A.; Tuchin, Valery V.; Yodh, Arjun G.; Mishin, Alexey A.; Peretochkin, Igor S.

1998-04-01

Relationships between decorrelation and depolarization of coherent light scattered by disordered media are examined by using the conception of the photon paths distribution functions. Analysis of behavior of the autocorrelation functions of the scattered field fluctuations and their polarization properties allows us to introduce generalized parameter of scattering media such as specific correlation time. Determination of specific correlation time has been carried out for phantom scattering media (water suspensions of polystyrene spheres). Results of statistical, correlation and polarization analysis of static and dynamic speckle patterns carried out in the experiments with human sclera with artificially controlled optical transmittance are presented. Some possibilities of applications of such polarization- correlation technique for monitoring and visualization of non- single scattering tissue structures are discussed.

Low-resolution mapping of the effective attenuation coefficient of the human head: a multidistance approach applied to high-density optical recordings

PubMed Central

Chiarelli, Antonio M.; Maclin, Edward L.; Low, Kathy A.; Fantini, Sergio; Fabiani, Monica; Gratton, Gabriele

2017-01-01

Abstract. Near infrared (NIR) light has been widely used for measuring changes in hemoglobin concentration in the human brain (functional NIR spectroscopy, fNIRS). fNIRS is based on the differential measurement and estimation of absorption perturbations, which, in turn, are based on correctly estimating the absolute parameters of light propagation. To do so, it is essential to accurately characterize the baseline optical properties of tissue (absorption and reduced scattering coefficients). However, because of the diffusive properties of the medium, separate determination of absorption and scattering across the head is challenging. The effective attenuation coefficient (EAC), which is proportional to the geometric mean of absorption and reduced scattering coefficients, can be estimated in a simpler fashion by multidistance light decay measurements. EAC mapping could be of interest for the scientific community because of its absolute information content, and because light propagation is governed by the EAC for source–detector distances exceeding 1 cm, which sense depths extending beyond the scalp and skull layers. Here, we report an EAC mapping procedure that can be applied to standard fNIRS recordings, yielding topographic maps with 2- to 3-cm resolution. Application to human data indicates the importance of venous sinuses in determining regional EAC variations, a factor often overlooked. PMID:28466026

Low-resolution mapping of the effective attenuation coefficient of the human head: a multidistance approach applied to high-density optical recordings.

PubMed

Chiarelli, Antonio M; Maclin, Edward L; Low, Kathy A; Fantini, Sergio; Fabiani, Monica; Gratton, Gabriele

2017-04-01

Near infrared (NIR) light has been widely used for measuring changes in hemoglobin concentration in the human brain (functional NIR spectroscopy, fNIRS). fNIRS is based on the differential measurement and estimation of absorption perturbations, which, in turn, are based on correctly estimating the absolute parameters of light propagation. To do so, it is essential to accurately characterize the baseline optical properties of tissue (absorption and reduced scattering coefficients). However, because of the diffusive properties of the medium, separate determination of absorption and scattering across the head is challenging. The effective attenuation coefficient (EAC), which is proportional to the geometric mean of absorption and reduced scattering coefficients, can be estimated in a simpler fashion by multidistance light decay measurements. EAC mapping could be of interest for the scientific community because of its absolute information content, and because light propagation is governed by the EAC for source-detector distances exceeding 1 cm, which sense depths extending beyond the scalp and skull layers. Here, we report an EAC mapping procedure that can be applied to standard fNIRS recordings, yielding topographic maps with 2- to 3-cm resolution. Application to human data indicates the importance of venous sinuses in determining regional EAC variations, a factor often overlooked.

Optical pathology of human brain metastasis of lung cancer using combined resonance Raman and spatial frequency spectroscopies

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Pu, Yang; Cheng, Gangge; Zhou, Lixin; Chen, Jun; Zhu, Ke; Alfano, Robert R.

2016-03-01

Raman spectroscopy has become widely used for diagnostic purpose of breast, lung and brain cancers. This report introduced a new approach based on spatial frequency spectra analysis of the underlying tissue structure at different stages of brain tumor. Combined spatial frequency spectroscopy (SFS), Resonance Raman (RR) spectroscopic method is used to discriminate human brain metastasis of lung cancer from normal tissues for the first time. A total number of thirty-one label-free micrographic images of normal and metastatic brain cancer tissues obtained from a confocal micro- Raman spectroscopic system synchronously with examined RR spectra of the corresponding samples were collected from the identical site of tissue. The difference of the randomness of tissue structures between the micrograph images of metastatic brain tumor tissues and normal tissues can be recognized by analyzing spatial frequency. By fitting the distribution of the spatial frequency spectra of human brain tissues as a Gaussian function, the standard deviation, σ, can be obtained, which was used to generate a criterion to differentiate human brain cancerous tissues from the normal ones using Support Vector Machine (SVM) classifier. This SFS-SVM analysis on micrograph images presents good results with sensitivity (85%), specificity (75%) in comparison with gold standard reports of pathology and immunology. The dual-modal advantages of SFS combined with RR spectroscopy method may open a new way in the neuropathology applications.

Real-Time Optical Diagnosis of the Rat Brain Exposed to a Laser-Induced Shock Wave: Observation of Spreading Depolarization, Vasoconstriction and Hypoxemia-Oligemia

PubMed Central

Sato, Shunichi; Kawauchi, Satoko; Okuda, Wataru; Nishidate, Izumi; Nawashiro, Hiroshi; Tsumatori, Gentaro

2014-01-01

Despite many efforts, the pathophysiology and mechanism of blast-induced traumatic brain injury (bTBI) have not yet been elucidated, partially due to the difficulty of real-time diagnosis and extremely complex factors determining the outcome. In this study, we topically applied a laser-induced shock wave (LISW) to the rat brain through the skull, for which real-time measurements of optical diffuse reflectance and electroencephalogram (EEG) were performed. Even under conditions showing no clear changes in systemic physiological parameters, the brain showed a drastic light scattering change accompanied by EEG suppression, which indicated the occurrence of spreading depression, long-lasting hypoxemia and signal change indicating mitochondrial energy impairment. Under the standard LISW conditions examined, hemorrhage and contusion were not apparent in the cortex. To investigate events associated with spreading depression, measurement of direct current (DC) potential, light scattering imaging and stereomicroscopic observation of blood vessels were also conducted for the brain. After LISW application, we observed a distinct negative shift in the DC potential, which temporally coincided with the transit of a light scattering wave, showing the occurrence of spreading depolarization and concomitant change in light scattering. Blood vessels in the brain surface initially showed vasodilatation for 3–4 min, which was followed by long-lasting vasoconstriction, corresponding to hypoxemia. Computer simulation based on the inverse Monte Carlo method showed that hemoglobin oxygen saturation declined to as low as ∼35% in the long-term hypoxemic phase. Overall, we found that topical application of a shock wave to the brain caused spreading depolarization/depression and prolonged severe hypoxemia-oligemia, which might lead to pathological conditions in the brain. Although further study is needed, our findings suggest that spreading depolarization/depression is one of the key events determining the outcome in bTBI. Furthermore, a rat exposed to an LISW(s) can be a reliable laboratory animal model for blast injury research. PMID:24416150

Detection of gastrointestinal cancer by elastic scattering and absorption spectroscopies with the Los Alamos Optical Biopsy System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mourant, J.R.; Boyer, J.; Johnson, T.M.

1995-03-01

The Los Alamos National Laboratory has continued the development of the Optical Biopsy System (OBS) for noninvasive, real-time in situ diagnosis of tissue pathologies. In proceedings of earlier SPIE conferences we reported on clinical measurements in the bladder, and we report here on recent results of clinical tests in the gastrointestinal tract. With the OBS, tissue pathologies are detected/diagnosed using spectral measurements of the elastic optical transport properties (scattering and absorption) of the tissue over a wide range of wavelengths. The use of elastic scattering as the key to optical tissue diagnostics in the OBS is based on the factmore » that many tissue pathologies, including a majority of cancer forms, exhibit significant architectural changes at the cellular and sub-cellular level. Since the cellular components that cause elastic scattering have dimensions typically on the order of visible to near-IR wavelengths, the elastic (Mie) scattering properties will be wavelength dependent. Thus, morphology and size changes can be expected to cause significant changes m an optical signature that is derived from the wavelength-dependence of elastic scattering. Additionally, the optical geometry of the OBS beneficially enhances its sensitivity for measuring absorption bands. The OBS employs a small fiber-optic probe that is amenable to use with any endoscope or catheter, or to direct surface examination, as well as interstitial needle insertion. Data acquistion/display time is <1 second.« less

Time-dependent photon migration imaging

NASA Astrophysics Data System (ADS)

Sevick, Eva M.; Wang, NaiGuang; Chance, Britton

1992-02-01

Recently, the application of both time- and frequency-resolved fluorescence techniques for the determination of photon migration characteristics in strongly scattering media has been used to characterize the optical properties in strongly scattering media. Specifically, Chance and coworkers have utilized measurement of photon migration characteristics to determine tissue hemoglobin absorbance and ultimately oxygenation status in homogeneous tissues. In this study, we present simulation results and experimental measurements for both techniques to show the capacity of time-dependent photon migration characteristics to image optically obscure absorbers located in strongly scattering media. The applications of time-dependent photon imaging in the biomedical community include imaging of light absorbing hematomas, tumors, hypoxic tissue volumes, and other tissue abnormalities. Herein, we show that the time-resolved parameter of mean photon path length, , and the frequency- resolved parameter of phase-shift, (theta) , can be used similarly to obtain three dimensional information of absorber position from two-dimensional measurements. Finally, we show that unlike imaging techniques that monitor the intensity of light without regard to the migration characteristics, the resolution of time-dependent photon migration measurements is enhanced by tissue scattering, further potentiating their use for biomedical imaging.

Impact of Neurodegenerative Diseases on Drug Binding to Brain Tissues: From Animal Models to Human Samples.

PubMed

Ugarte, Ana; Corbacho, David; Aymerich, María S; García-Osta, Ana; Cuadrado-Tejedor, Mar; Oyarzabal, Julen

2018-04-19

Drug efficacy in the central nervous system (CNS) requires an additional step after crossing the blood-brain barrier. Therapeutic agents must reach their targets in the brain to modulate them; thus, the free drug concentration hypothesis is a key parameter for in vivo pharmacology. Here, we report the impact of neurodegeneration (Alzheimer's disease (AD) and Parkinson's disease (PD) compared with healthy controls) on the binding of 10 known drugs to postmortem brain tissues from animal models and humans. Unbound drug fractions, for some drugs, are significantly different between healthy and injured brain tissues (AD or PD). In addition, drugs binding to brain tissues from AD and PD animal models do not always recapitulate their binding to the corresponding human injured brain tissues. These results reveal potentially relevant implications for CNS drug discovery.

Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields.

PubMed

Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

2016-06-21

An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform's size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke's brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields

NASA Astrophysics Data System (ADS)

Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

2016-06-01

An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform’s size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke’s brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

Temperature-dependent elastic properties of brain tissues measured with the shear wave elastography method.

PubMed

Liu, Yan-Lin; Li, Guo-Yang; He, Ping; Mao, Ze-Qi; Cao, Yanping

2017-01-01

Determining the mechanical properties of brain tissues is essential in such cases as the surgery planning and surgical training using virtual reality based simulators, trauma research and the diagnosis of some diseases that alter the elastic properties of brain tissues. Here, we suggest a protocol to measure the temperature-dependent elastic properties of brain tissues in physiological saline using the shear wave elastography method. Experiments have been conducted on six porcine brains. Our results show that the shear moduli of brain tissues decrease approximately linearly with a slope of -0.041±0.006kPa/°C when the temperature T increases from room temperature (~23°C) to body temperature (~37°C). A case study has been further conducted which shows that the shear moduli are insensitive to the temperature variation when T is in the range of 37 to 43°C and will increase when T is higher than 43°C. With the present experimental setup, temperature-dependent elastic properties of brain tissues can be measured in a simulated physiological environment and a non-destructive manner. Thus the method suggested here offers a unique tool for the mechanical characterization of brain tissues with potential applications in brain biomechanics research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms

PubMed Central

Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S.

2017-01-01

While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17–16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models. PMID:28582392

Sequential weighted Wiener estimation for extraction of key tissue parameters in color imaging: a phantom study

NASA Astrophysics Data System (ADS)

Chen, Shuo; Lin, Xiaoqian; Zhu, Caigang; Liu, Quan

2014-12-01

Key tissue parameters, e.g., total hemoglobin concentration and tissue oxygenation, are important biomarkers in clinical diagnosis for various diseases. Although point measurement techniques based on diffuse reflectance spectroscopy can accurately recover these tissue parameters, they are not suitable for the examination of a large tissue region due to slow data acquisition. The previous imaging studies have shown that hemoglobin concentration and oxygenation can be estimated from color measurements with the assumption of known scattering properties, which is impractical in clinical applications. To overcome this limitation and speed-up image processing, we propose a method of sequential weighted Wiener estimation (WE) to quickly extract key tissue parameters, including total hemoglobin concentration (CtHb), hemoglobin oxygenation (StO2), scatterer density (α), and scattering power (β), from wide-band color measurements. This method takes advantage of the fact that each parameter is sensitive to the color measurements in a different way and attempts to maximize the contribution of those color measurements likely to generate correct results in WE. The method was evaluated on skin phantoms with varying CtHb, StO2, and scattering properties. The results demonstrate excellent agreement between the estimated tissue parameters and the corresponding reference values. Compared with traditional WE, the sequential weighted WE shows significant improvement in the estimation accuracy. This method could be used to monitor tissue parameters in an imaging setup in real time.

Brief Report: The Role of National Brain and Tissue Banks in Research on Autism and Developmental Disorders.

ERIC Educational Resources Information Center

Zielke, H. Ronald; And Others

1996-01-01

This paper describes the establishment and work of two brain and tissue banks, which collect brain and other tissues from newly deceased individuals with autism and make these tissues available to researchers. Issues in tissue collection are identified, including the importance of advance planning, religious concerns of families, and the need for…

A strategy to measure electrophysiological changes with photoacoustic imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sepela, Rebecka J.; Sherlock, Benjamin E.; Tian, Lin; Marcu, Laura; Sack, Jon

2017-03-01

Photoacoustic imaging is an emerging technology capable of both functional and structural biological imaging. Absorption and scattering in tissue limit the penetration depth of conventional microscopy techniques to <1mm. Photoacoustic imaging however, can offer high-resolution and contrast at depths of several centimeters. Though functional imaging of endogenous contrast agents, such as hemoglobin, is widely implemented, currently photoacoustic imaging is unable to functionally report electrophysiological changes within cells. We aim to develop photoacoustic contrast agents to fulfill this need. Cells throughout the brain and body create electrical signals using ion channel proteins. These proteins undergo structural changes to regulate the flux of salt ions into the cell. We have recently developed ion channel activity tracers that dissociate from ion channels after the protein changes structure. By conjugating the tracer to dyes that are sensitive to changes in their chemical environment, we can detect tracer dissociation and therefore ion channel activity. We are exploring whether a similar mechanism can create photoacoustic signal intensity changes. To test if the environmental sensitivity of the dye is photoacoustically distinguishable, we imaged the dye in different solvent backgrounds. We report that manipulation of the chemical environment of the contrast dye results in robust changes in photoacoustic properties. We are working to capture photoacoustic signal changes that occur when ion channel proteins activate using live cell imaging. This technology could permit photoacoustic imaging of electrophysiological dynamics in deep tissue, such as the brain. Further optimization of this technology could lead to concurrent imaging of neural activity and hemodynamic responses, a crucial step towards understanding neurovascular coupling in the brain.

Quantitative fluorescence and elastic scattering tissue polarimetry using an Eigenvalue calibrated spectroscopic Mueller matrix system.

PubMed

Soni, Jalpa; Purwar, Harsh; Lakhotia, Harshit; Chandel, Shubham; Banerjee, Chitram; Kumar, Uday; Ghosh, Nirmalya

2013-07-01

A novel spectroscopic Mueller matrix system has been developed and explored for both fluorescence and elastic scattering polarimetric measurements from biological tissues. The 4 × 4 Mueller matrix measurement strategy is based on sixteen spectrally resolved (λ = 400 - 800 nm) measurements performed by sequentially generating and analyzing four elliptical polarization states. Eigenvalue calibration of the system ensured high accuracy of Mueller matrix measurement over a broad wavelength range, either for forward or backscattering geometry. The system was explored for quantitative fluorescence and elastic scattering spectroscopic polarimetric studies on normal and precancerous tissue sections from human uterine cervix. The fluorescence spectroscopic Mueller matrices yielded an interesting diattenuation parameter, exhibiting differences between normal and precancerous tissues.

Probability density function formalism for optical coherence tomography signal analysis: a controlled phantom study.

PubMed

Weatherbee, Andrew; Sugita, Mitsuro; Bizheva, Kostadinka; Popov, Ivan; Vitkin, Alex

2016-06-15

The distribution of backscattered intensities as described by the probability density function (PDF) of tissue-scattered light contains information that may be useful for tissue assessment and diagnosis, including characterization of its pathology. In this Letter, we examine the PDF description of the light scattering statistics in a well characterized tissue-like particulate medium using optical coherence tomography (OCT). It is shown that for low scatterer density, the governing statistics depart considerably from a Gaussian description and follow the K distribution for both OCT amplitude and intensity. The PDF formalism is shown to be independent of the scatterer flow conditions; this is expected from theory, and suggests robustness and motion independence of the OCT amplitude (and OCT intensity) PDF metrics in the context of potential biomedical applications.

Prediction of brain deformations and risk of traumatic brain injury due to closed-head impact: quantitative analysis of the effects of boundary conditions and brain tissue constitutive model.

PubMed

Wang, Fang; Han, Yong; Wang, Bingyu; Peng, Qian; Huang, Xiaoqun; Miller, Karol; Wittek, Adam

2018-05-12

In this study, we investigate the effects of modelling choices for the brain-skull interface (layers of tissues between the brain and skull that determine boundary conditions for the brain) and the constitutive model of brain parenchyma on the brain responses under violent impact as predicted using computational biomechanics model. We used the head/brain model from Total HUman Model for Safety (THUMS)-extensively validated finite element model of the human body that has been applied in numerous injury biomechanics studies. The computations were conducted using a well-established nonlinear explicit dynamics finite element code LS-DYNA. We employed four approaches for modelling the brain-skull interface and four constitutive models for the brain tissue in the numerical simulations of the experiments on post-mortem human subjects exposed to violent impacts reported in the literature. The brain-skull interface models included direct representation of the brain meninges and cerebrospinal fluid, outer brain surface rigidly attached to the skull, frictionless sliding contact between the brain and skull, and a layer of spring-type cohesive elements between the brain and skull. We considered Ogden hyperviscoelastic, Mooney-Rivlin hyperviscoelastic, neo-Hookean hyperviscoelastic and linear viscoelastic constitutive models of the brain tissue. Our study indicates that the predicted deformations within the brain and related brain injury criteria are strongly affected by both the approach of modelling the brain-skull interface and the constitutive model of the brain parenchyma tissues. The results suggest that accurate prediction of deformations within the brain and risk of brain injury due to violent impact using computational biomechanics models may require representation of the meninges and subarachnoidal space with cerebrospinal fluid in the model and application of hyperviscoelastic (preferably Ogden-type) constitutive model for the brain tissue.

Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats.

PubMed

Zhang, Na; Cheng, Gen-Yang; Liu, Xian-Zhi; Zhang, Feng-Jiang

2014-05-01

To investigate the effect of acute renal ischemia reperfusion on brain tissue. Fourty eight rats were randomly divided into four groups (n=12): sham operation group, 30 min ischemia 60 min reperfusion group, 60 min ischemia 60 min reperfusion group, and 120 min ischemia 60 min reperfusion group. The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors. Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time. The detection at the molecular level showed decreased Bcl-2 expression, increased Bax expression, upregulated expression of NF-κB and its downstream factor COX-2/PGE2. Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

HIV-1 Phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

PubMed Central

Lamers, Susanna L.; Gray, Rebecca R.; Salemi, Marco; Huysentruyt, Leanne C.; McGrath, Michael

2010-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that 1) HIV-1 is clearly capable of migrating out of the brain, 2) the meninges are the most likely primary transport tissues, and 3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. PMID:21055482

Combined Bisulfite Restriction Analysis for brain tissue identification.

PubMed

Samsuwan, Jarunya; Muangsub, Tachapol; Yanatatsaneejit, Pattamawadee; Mutirangura, Apiwat; Kitkumthorn, Nakarin

2018-05-01

According to the tissue-specific methylation database (doi: 10.1016/j.gene.2014.09.060), methylation at CpG locus cg03096975 in EML2 has been preliminarily proven to be specific to brain tissue. In this study, we enlarged sample size and developed a technique for identifying brain tissue in aged samples. Combined Bisulfite Restriction Analysis-for EML2 (COBRA-EML2) technique was established and validated in various organ samples obtained from 108 autopsies. In addition, this technique was also tested for its reliability, minimal DNA concentration detected, and use in aged samples and in samples obtained from specific brain compartments and spinal cord. COBRA-EML2 displayed 100% sensitivity and specificity for distinguishing brain tissue from other tissues, showed high reliability, was capable of detecting minimal DNA concentration (0.015ng/μl), could be used for identifying brain tissue in aged samples. In summary, COBRA-EML2 is a technique to identify brain tissue. This analysis is useful in criminal cases since it can identify the vital organ tissues from small samples acquired from criminal scenes. The results from this analysis can be counted as a medical and forensic marker supporting criminal investigations, and as one of the evidences in court rulings. Copyright © 2018 Elsevier B.V. All rights reserved.

Optical diagnostics based on elastic scattering: Recent clinical demonstrations with the Los Alamos Optical Biopsy System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bigio, I.J.; Loree, T.R.; Mourant, J.

1993-08-01

A non-invasive diagnostic tool that could identify malignancy in situ and in real time would have a major impact on the detection and treatment of cancer. We have developed and are testing early prototypes of an optical biopsy system (OBS) for detection of cancer and other tissue pathologies. The OBS invokes a unique approach to optical diagnosis of tissue pathologies based on the elastic scattering properties, over a wide range of wavelengths, of the microscopic structure of the tissue. The use of elastic scattering as the key to optical tissue diagnostics in the OBS is based on the fact thatmore » many tissue pathologies, including a majority of cancer forms, manifest significant architectural changes at the cellular and sub-cellular level. Since the cellular components that cause elastic scattering have dimensions typically on the order of visible to near-IR wavelengths, the elastic (Mie) scattering properties will be strongly wavelength dependent. Thus, morphology and size changes can be expected to cause significant changes in an optical signature that is derived from the wavelength dependence of elastic scattering. The data acquisition and storage/display time with the OBS instrument is {approximately}1 second. Thus, in addition to the reduced invasiveness of this technique compared with current state-of-the-art methods (surgical biopsy and pathology analysis), the OBS offers the possibility of impressively faster diagnostic assessment. The OBS employs a small fiber-optic probe that is amenable to use with any endoscope, catheter or hypodermic, or to direct surface examination (e.g. as in skin cancer or cervical cancer). It has been tested in vitro on animal and human tissue samples, and clinical testing in vivo is currently in progress.« less

Development and Application of Chemical Probes for Vibrational Imaging by Stimulated Raman Scattering

NASA Astrophysics Data System (ADS)

Hu, Fanghao

During the last decade, Raman microscopy is experiencing rapid development and increasingly applied in biological and medical systems. Especially, stimulated Raman scattering (SRS) microscopy, which significantly improves the sensitivity of Raman scattering through stimulated emission, has allowed direct visualization of many species that are previously challenging with conventional fluorescence imaging. Compared to fluorescence, SRS imaging requires no label or small label on the target molecule, thus with minimal perturbation to the molecule of interest. Moreover, Raman scattering is free from complicated photophysical and photochemical processes such as photobleaching, and has intrinsically narrower linewidth than fluorescence emission. This allows multiplexed Raman imaging with minimal spectral crosstalk and excellent photo-stability. To achieve the full potential of Raman microscopy, vibrational probes have been developed for Raman imaging. Multiple Raman probes with a few atoms in size are applied in Raman imaging with high sensitivity and specificity. An overview of both fluorescence and Raman microscopy and their imaging probes is given in Chapter 1 with a brief discussion on the SRS theory. Built on the current progress of Raman microscopy and vibrational probes, I write on my research in the development of carbon-deuterium, alkyne and nitrile probes for visualizing choline metabolism (Chapter 2), glucose uptake activity (Chapter 3), complex brain metabolism (Chapter 4) and polymeric nanoparticles (Chapter 5) in live cells and tissues, as well as the development of polyyne-based vibrational probes for super-multiplexed imaging, barcoding and analysis (Chapter 6).

Non-invasive detection and quantification of brain microvascular deficits by near-infrared spectroscopy in a rat model of Vascular Cognitive Impairment

NASA Astrophysics Data System (ADS)

Hallacoglu, Bertan; Sassaroli, Angelo M.; Rosenberg, Irwin H.; Troen, Aron; Fantini, Sergio

2011-02-01

Structural abnormalities in brain microvasculature are commonly associated with Alzheimer's Disease and other dementias. However, the extent to which structural microvascular abnormalities cause functional impairments in brain circulation and thereby to cognitive impairment is unclear. Non-invasive, near-infrared spectroscopy (NIRS) methods can be used to determine the absolute hemoglobin concentration and saturation in brain tissue, from which additional parameters such as cerebral blood volume (a theoretical correlate of brain microvascular density) can be derived. Validating such NIRS parameters in animal models, and understanding their relationship to cognitive function is an important step in the ultimate application of these methods to humans. To this end we applied a non-invasive multidistance NIRS method to determine the absolute concentration and saturation of cerebral hemoglobin in rat, by separately measuring absorption and reduced scattering coefficients without relying on pre- or post-correction factors. We applied this method to study brain circulation in folate deficient rats, which express brain microvascular pathology1 and which we have shown to develop cognitive impairment.2 We found absolute brain hemoglobin concentration ([HbT]) and oxygen saturation (StO2) to be significantly lower in folate deficient rats (n=6) with respect to control rats (n=5) (for [HbT]: 73+/-10 μM vs. 95+/-14 μM for StO2: 55%+/-7% vs. 66% +/-4%), implicating microvascular pathology and diminished oxygen delivery as a mechanism of cognitive impairment. More generally, our study highlights how noninvasive, absolute NIRS measurements can provide unique insight into the pathophysiology of Vascular Cognitive Impairment. Applying this method to this and other rat models of cognitive impairment will help to validate physiologically meaningful NIRS parameters for the ultimate goal of studying cerebral microvascular disease and cognitive decline in humans.

Tissue polarimetry: concepts, challenges, applications, and outlook.

PubMed

Ghosh, Nirmalya; Vitkin, I Alex

2011-11-01

Polarimetry has a long and successful history in various forms of clear media. Driven by their biomedical potential, the use of the polarimetric approaches for biological tissue assessment has also recently received considerable attention. Specifically, polarization can be used as an effective tool to discriminate against multiply scattered light (acting as a gating mechanism) in order to enhance contrast and to improve tissue imaging resolution. Moreover, the intrinsic tissue polarimetry characteristics contain a wealth of morphological and functional information of potential biomedical importance. However, in a complex random medium-like tissue, numerous complexities due to multiple scattering and simultaneous occurrences of many scattering and polarization events present formidable challenges both in terms of accurate measurements and in terms of analysis of the tissue polarimetry signal. In order to realize the potential of the polarimetric approaches for tissue imaging and characterization/diagnosis, a number of researchers are thus pursuing innovative solutions to these challenges. In this review paper, we summarize these and other issues pertinent to the polarized light methodologies in tissues. Specifically, we discuss polarized light basics, Stokes-Muller formalism, methods of polarization measurements, polarized light modeling in turbid media, applications to tissue imaging, inverse analysis for polarimetric results quantification, applications to quantitative tissue assessment, etc.

Robotic multimodality stereotactic brain tissue identification: work in progress

NASA Technical Reports Server (NTRS)

Andrews, R.; Mah, R.; Galvagni, A.; Guerrero, M.; Papasin, R.; Wallace, M.; Winters, J.

1997-01-01

Real-time identification of tissue would improve procedures such as stereotactic brain biopsy (SBX), functional and implantation neurosurgery, and brain tumor excision. To standard SBX equipment has been added: (1) computer-controlled stepper motors to drive the biopsy needle/probe precisely; (2) multiple microprobes to track tissue density, detect blood vessels and changes in blood flow, and distinguish the various tissues being penetrated; (3) neural net learning programs to allow real-time comparisons of current data with a normative data bank; (4) three-dimensional graphic displays to follow the probe as it traverses brain tissue. The probe can differentiate substances such as pig brain, differing consistencies of the 'brain-like' foodstuff tofu, and gels made to simulate brain, as well as detect blood vessels imbedded in these substances. Multimodality probes should improve the safety, efficacy, and diagnostic accuracy of SBX and other neurosurgical procedures.

A family of hyperelastic models for human brain tissue

NASA Astrophysics Data System (ADS)

Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

2017-09-01

Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián; Alfano, Robert

2016-01-01

The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer's disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional-vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests that THz-absorption modes may be used as an AD biomarker fingerprint in brain, and that THz-TDS is a promising technique for early diagnosis of AD.

Evaluation of Shifted Excitation Raman Difference Spectroscopy and Comparison to Computational Background Correction Methods Applied to Biochemical Raman Spectra.

PubMed

Cordero, Eliana; Korinth, Florian; Stiebing, Clara; Krafft, Christoph; Schie, Iwan W; Popp, Jürgen

2017-07-27

Raman spectroscopy provides label-free biochemical information from tissue samples without complicated sample preparation. The clinical capability of Raman spectroscopy has been demonstrated in a wide range of in vitro and in vivo applications. However, a challenge for in vivo applications is the simultaneous excitation of auto-fluorescence in the majority of tissues of interest, such as liver, bladder, brain, and others. Raman bands are then superimposed on a fluorescence background, which can be several orders of magnitude larger than the Raman signal. To eliminate the disturbing fluorescence background, several approaches are available. Among instrumentational methods shifted excitation Raman difference spectroscopy (SERDS) has been widely applied and studied. Similarly, computational techniques, for instance extended multiplicative scatter correction (EMSC), have also been employed to remove undesired background contributions. Here, we present a theoretical and experimental evaluation and comparison of fluorescence background removal approaches for Raman spectra based on SERDS and EMSC.

Evaluation of Shifted Excitation Raman Difference Spectroscopy and Comparison to Computational Background Correction Methods Applied to Biochemical Raman Spectra

PubMed Central

Cordero, Eliana; Korinth, Florian; Stiebing, Clara; Krafft, Christoph; Schie, Iwan W.; Popp, Jürgen

2017-01-01

Raman spectroscopy provides label-free biochemical information from tissue samples without complicated sample preparation. The clinical capability of Raman spectroscopy has been demonstrated in a wide range of in vitro and in vivo applications. However, a challenge for in vivo applications is the simultaneous excitation of auto-fluorescence in the majority of tissues of interest, such as liver, bladder, brain, and others. Raman bands are then superimposed on a fluorescence background, which can be several orders of magnitude larger than the Raman signal. To eliminate the disturbing fluorescence background, several approaches are available. Among instrumentational methods shifted excitation Raman difference spectroscopy (SERDS) has been widely applied and studied. Similarly, computational techniques, for instance extended multiplicative scatter correction (EMSC), have also been employed to remove undesired background contributions. Here, we present a theoretical and experimental evaluation and comparison of fluorescence background removal approaches for Raman spectra based on SERDS and EMSC. PMID:28749450

Effects of Antioxidant N-acetylcysteine Against Paraquat-Induced Oxidative Stress in Vital Tissues of Mice

PubMed Central

Ortiz, Maricelly Santiago; Forti, Kevin Muñoz; Suárez Martinez, Edu B.; Muñoz, Lenin Godoy; Husain, Kazim

2016-01-01

Paraquat (PQ) is a commonly used herbicide that induces oxidative stress via reactive oxygen species (ROS) generation. This study aimed to investigate the effects of the antioxidant N-acetylcysteine (NAC) against PQ-induced oxidative stress in mice. Male Balb/C mice (24) were randomly divided into 4 groups and treated for 3 weeks: 1) control (saline), 2) NAC (0.5% in diet), 3) PQ (20 mg/kg, IP) and 4) combination (PQ + NAC). Afterwards mice were sacrificed and oxidative stress markers were analyzed. Our data showed no significant change in serum antioxidant capacity. PQ enhanced lipid peroxidation (MDA) levels in liver tissue compared to control whereas NAC decreased MDA levels (p<0.05). NAC significantly increased MDA in brain tissue (p<0.05). PQ significantly depleted glutathione (GSH) levels in liver (p=0.001) and brain tissue (p<0.05) but non-significant GSH depletion in lung tissue. NAC counteracted PQ, showing a moderate increase GSH levels in liver and brain tissues. PQ significantly increased 8-oxodeoxyguanosine (8-OH-dG) levels (p<0.05) in liver tissue compared to control without a significant change in brain tissue. NAC treatment ameliorated PQ-induced oxidative DNA damage in the liver tissue. PQ significantly decreased the relative mtDNA amplification and increased the frequency of lesions in liver and brain tissue (p<0.0001), while NAC restored the DNA polymerase activity in liver tissue but not in brain tissue. In conclusion, PQ induced lipid peroxidation, oxidative nuclear DNA and mtDNA damage in liver tissues and depleted liver and brain GSH levels. NAC supplementation ameliorated the PQ-induced oxidative stress response in liver tissue of mice. PMID:27398384

BECon: a tool for interpreting DNA methylation findings from blood in the context of brain.

PubMed

Edgar, R D; Jones, M J; Meaney, M J; Turecki, G; Kobor, M S

2017-08-01

Tissue differences are one of the largest contributors to variability in the human DNA methylome. Despite the tissue-specific nature of DNA methylation, the inaccessibility of human brain samples necessitates the frequent use of surrogate tissues such as blood, in studies of associations between DNA methylation and brain function and health. Results from studies of surrogate tissues in humans are difficult to interpret in this context, as the connection between blood-brain DNA methylation is tenuous and not well-documented. Here, we aimed to provide a resource to the community to aid interpretation of blood-based DNA methylation results in the context of brain tissue. We used paired samples from 16 individuals from three brain regions and whole blood, run on the Illumina 450 K Human Methylation Array to quantify the concordance of DNA methylation between tissues. From these data, we have made available metrics on: the variability of cytosine-phosphate-guanine dinucleotides (CpGs) in our blood and brain samples, the concordance of CpGs between blood and brain, and estimations of how strongly a CpG is affected by cell composition in both blood and brain through the web application BECon (Blood-Brain Epigenetic Concordance; https://redgar598.shinyapps.io/BECon/). We anticipate that BECon will enable biological interpretation of blood-based human DNA methylation results, in the context of brain.

TU-G-210-00: Treatment Planning Strategies, Modeling, Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such asmore » the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)« less

TU-G-210-03: Acoustic Simulations in Transcranial MRgFUS: Treatment Prediction and Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vyas, U.

Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such asmore » the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO - An Integrative Approach to Model-Based Treatment Planning of Liver FUS Urvi Vyas – Acoustic Simulations in Transcranial MRgFUS: Treatment Prediction and Analysis Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)« less

Metabolomic Analysis of Anti-Hypoxia and Anti-anxiety Effects of Fu Fang Jin Jing Oral Liquid

PubMed Central

Guan, Shuhong; Feng, Ruihong; Zhang, Hui; Liu, Qiuhong; Sun, Peng; Lin, Donghai; Zhang, Naixia; Shen, Jun

2013-01-01

Background Herba Rhodiolae is a traditional Chinese medicine used by the Tibetan people for treating hypoxia related diseases such as anxiety. Based on the previous work, we developed and patented an anti-anxiety herbal formula Fu Fang Jin Jing Oral Liquid (FJJOL) with Herba Rhodiolae as a chief ingredient. In this study, the anti-hypoxia and anti-anxiety effects of FJJOL in a high altitude forced-swimming mouse model with anxiety symptoms will be elucidated by NMR-based metabolomics. Methods In our experiments, the mice were divided randomly into four groups as flatland group, high altitude saline-treated group, high altitude FJJOL-treated group, and high altitude diazepam-treated group. To cause anxiety effects and hypoxic defects, a combination use of oxygen level decreasing (hypobaric cabin) and oxygen consumption increasing (exhaustive swimming) were applied to mice. After a three-day experimental handling, aqueous metabolites of mouse brain tissues were extracted and then subjected to NMR analysis. The therapeutic effects of FJJOL on the hypobaric hypoxia mice with anxiety symptoms were verified. Results Upon hypoxic exposure, both energy metabolism defects and disorders of functional metabolites in brain tissues of mice were observed. PCA, PLS-DA and OPLS-DA scatter plots revealed a clear group clustering for metabolic profiles in the hypoxia versus normoxia samples. After a three-day treatment with FJJOL, significant rescue effects on energy metabolism were detected, and levels of ATP, fumarate, malate and lactate in brain tissues of hypoxic mice recovered. Meanwhile, FJJOL also up-regulated the neurotransmitter GABA, and the improvement of anxiety symptoms was highly related to this effect. Conclusions FJJOL ameliorated hypobaric hypoxia effects by regulating energy metabolism, choline metabolism, and improving the symptoms of anxiety. The anti-anxiety therapeutic effects of FJJOL were comparable to the conventional anti-anxiety drug diazepam on the hypobaric hypoxia mice. FJJOL might serve as an alternative therapy for the hypoxia and anxiety disorders. PMID:24205180

Metabolomic analysis of anti-hypoxia and anti-anxiety effects of Fu Fang Jin Jing Oral Liquid.

PubMed

Liu, Xia; Zhu, Wei; Guan, Shuhong; Feng, Ruihong; Zhang, Hui; Liu, Qiuhong; Sun, Peng; Lin, Donghai; Zhang, Naixia; Shen, Jun

2013-01-01

Herba Rhodiolae is a traditional Chinese medicine used by the Tibetan people for treating hypoxia related diseases such as anxiety. Based on the previous work, we developed and patented an anti-anxiety herbal formula Fu Fang Jin Jing Oral Liquid (FJJOL) with Herba Rhodiolae as a chief ingredient. In this study, the anti-hypoxia and anti-anxiety effects of FJJOL in a high altitude forced-swimming mouse model with anxiety symptoms will be elucidated by NMR-based metabolomics. In our experiments, the mice were divided randomly into four groups as flatland group, high altitude saline-treated group, high altitude FJJOL-treated group, and high altitude diazepam-treated group. To cause anxiety effects and hypoxic defects, a combination use of oxygen level decreasing (hypobaric cabin) and oxygen consumption increasing (exhaustive swimming) were applied to mice. After a three-day experimental handling, aqueous metabolites of mouse brain tissues were extracted and then subjected to NMR analysis. The therapeutic effects of FJJOL on the hypobaric hypoxia mice with anxiety symptoms were verified. Upon hypoxic exposure, both energy metabolism defects and disorders of functional metabolites in brain tissues of mice were observed. PCA, PLS-DA and OPLS-DA scatter plots revealed a clear group clustering for metabolic profiles in the hypoxia versus normoxia samples. After a three-day treatment with FJJOL, significant rescue effects on energy metabolism were detected, and levels of ATP, fumarate, malate and lactate in brain tissues of hypoxic mice recovered. Meanwhile, FJJOL also up-regulated the neurotransmitter GABA, and the improvement of anxiety symptoms was highly related to this effect. FJJOL ameliorated hypobaric hypoxia effects by regulating energy metabolism, choline metabolism, and improving the symptoms of anxiety. The anti-anxiety therapeutic effects of FJJOL were comparable to the conventional anti-anxiety drug diazepam on the hypobaric hypoxia mice. FJJOL might serve as an alternative therapy for the hypoxia and anxiety disorders.

Wavefront shaping using a deformable mirror for focusing inside optical tissue phantoms

NASA Astrophysics Data System (ADS)

Gomes, Ricardo; Coelho, João. M. P.; Gabriel, Ana; Vieira, Pedro; Oliveira Silva, Catarina; Reis, Catarina

2014-08-01

Although light has long being used in medicine, scattering always hindered its use. This study intends to evolve into three different frontlines: development of methodologies to concentrate light inside biological tissues, development of an optical tissue phantom and development of multifunctional gold nanoparticles with therapeutic potential for targeting anticancer drug delivery. The impact of the scattering agent (milk) concentration in the measured wavefront and spot radius is analyzed. Wavefront correction proves to be efficient in overcoming the scattering effect in the different phantoms. Future studies for developing a photodynamic approach under near-infrared wavelength are now in progress and will be further presented.

Optical absorption and scattering spectra of pathological stomach tissues

NASA Astrophysics Data System (ADS)

Giraev, K. M.; Ashurbekov, N. A.; Lakhina, M. A.

2011-03-01

Diffuse reflection spectra of biotissues in vivo and transmission and reflection coefficients for biotissues in vitro are measured over 300-800 nm. These data are used to determine the spectral absorption and scattering indices and the scattering anisotropy factor for stomach mucous membranes under normal and various pathological conditions (chronic atrophic and ulcerous defects, malignant neoplasms). The most importan tphysiological (hemodynamic and oxygenation levels) and structural-morphological (scatterer size and density) parameters are also determined. The results of a morphofunctional study correlate well with the optical properties and are consistent with data from a histomorphological analysis of the corresponding tissues.

Lung cancer diagnosis with quantitative DIC microscopy and support vector machine

NASA Astrophysics Data System (ADS)

Zheng, Longfei; Cai, Shuangshuang; Zeng, Bixin; Xu, Min

2017-01-01

We report the study of lung squamous cell carcinoma diagnosis using the TI-DIC microscopy and the scattering-phase theorem. The spatially resolved optical properties of tissue are computed from the 2D phase map via the scattering-phase theorem. The scattering coefficient, the reduced scattering coefficient, and the anisotropy factor are all found to increase with the grade of lung cancer. The retrieved optical parameters are shown to distinguish cancer cases from the normal cases with high accuracy. This label-free microscopic approach applicable to fresh tissues may be promising for in situ rapid cancer diagnosis.

Characterization of scatter in digital mammography from use of Monte Carlo simulations and comparison to physical measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leon, Stephanie M., E-mail: Stephanie.Leon@uth.tmc.edu; Wagner, Louis K.; Brateman, Libby F.

2014-11-01

Purpose: Monte Carlo simulations were performed with the goal of verifying previously published physical measurements characterizing scatter as a function of apparent thickness. A secondary goal was to provide a way of determining what effect tissue glandularity might have on the scatter characteristics of breast tissue. The overall reason for characterizing mammography scatter in this research is the application of these data to an image processing-based scatter-correction program. Methods: MCNPX was used to simulate scatter from an infinitesimal pencil beam using typical mammography geometries and techniques. The spreading of the pencil beam was characterized by two parameters: mean radial extentmore » (MRE) and scatter fraction (SF). The SF and MRE were found as functions of target, filter, tube potential, phantom thickness, and the presence or absence of a grid. The SF was determined by separating scatter and primary by the angle of incidence on the detector, then finding the ratio of the measured scatter to the total number of detected events. The accuracy of the MRE was determined by placing ring-shaped tallies around the impulse and fitting those data to the point-spread function (PSF) equation using the value for MRE derived from the physical measurements. The goodness-of-fit was determined for each data set as a means of assessing the accuracy of the physical MRE data. The effect of breast glandularity on the SF, MRE, and apparent tissue thickness was also considered for a limited number of techniques. Results: The agreement between the physical measurements and the results of the Monte Carlo simulations was assessed. With a grid, the SFs ranged from 0.065 to 0.089, with absolute differences between the measured and simulated SFs averaging 0.02. Without a grid, the range was 0.28–0.51, with absolute differences averaging −0.01. The goodness-of-fit values comparing the Monte Carlo data to the PSF from the physical measurements ranged from 0.96 to 1.00 with a grid and 0.65 to 0.86 without a grid. Analysis of the data suggested that the nongrid data could be better described by a biexponential function than the single exponential used here. The simulations assessing the effect of breast composition on SF and MRE showed only a slight impact on these quantities. When compared to a mix of 50% glandular/50% adipose tissue, the impact of substituting adipose or glandular breast compositions on the apparent thickness of the tissue was about 5%. Conclusions: The findings show agreement between the physical measurements published previously and the Monte Carlo simulations presented here; the resulting data can therefore be used more confidently for an application such as image processing-based scatter correction. The findings also suggest that breast composition does not have a major impact on the scatter characteristics of breast tissue. Application of the scatter data to the development of a scatter-correction software program can be simplified by ignoring the variations in density among breast tissues.« less

Alzheimer's disease imaging biomarkers using small-angle x-ray scattering

NASA Astrophysics Data System (ADS)

Choi, Mina; Alam, Nadia; Dahal, Eshan; Ghammraoui, Bahaa; Badano, Aldo

2016-03-01

There is a need for novel imaging techniques for the earlier detection of Alzheimer's disease (AD). Two hallmarks of AD are amyloid beta (Aβ) plaques and tau tangles that are formed in the brain. Well-characterized x-ray cross sections of Aβ and tau proteins in a variety of structural states could potentially be used as AD biomarkers for small-angle x-ray scattering (SAXS) imaging without the need for injectable probes or contrast agents. First, however, the protein structures must be controlled and measured to determine accurate biomarkers for SAXS imaging. Here we report SAXS measurements of Aβ42 and tau352 in a 50% dimethyl sulfoxide (DMSO) solution in which these proteins are believed to remain monomeric because of the stabilizing interaction of DMSO solution. Our SAXS analysis showed the aggregation of both proteins. In particular, we found that the aggregation of Aβ42 slowly progresses with time in comparison to tau352 that aggregates at a faster rate and reaches a steady-state. Furthermore, the measured signals were compared to the theoretical SAXS profiles of Aβ42 monomer, Aβ42 fibril, and tau352 that were computed from their respective protein data bank structures. We have begun the work to systematically control the structural states of these proteins in vitro using various solvent conditions. Our future work is to utilize the distinct SAXS profiles of various structural states of Aβ and tau to build a library of signals of interest for SAXS imaging in brain tissue.

Optical characterization of pancreatic normal and tumor tissues with double integrating sphere system

NASA Astrophysics Data System (ADS)

Kiris, Tugba; Akbulut, Saadet; Kiris, Aysenur; Gucin, Zuhal; Karatepe, Oguzhan; Bölükbasi Ates, Gamze; Tabakoǧlu, Haşim Özgür

2015-03-01

In order to develop minimally invasive, fast and precise diagnostic and therapeutic methods in medicine by using optical methods, first step is to examine how the light propagates, scatters and transmitted through medium. So as to find out appropriate wavelengths, it is required to correctly determine the optical properties of tissues. The aim of this study is to measure the optical properties of both cancerous and normal ex-vivo pancreatic tissues. Results will be compared to detect how cancerous and normal tissues respond to different wavelengths. Double-integrating-sphere system and computational technique inverse adding doubling method (IAD) were used in the study. Absorption and reduced scattering coefficients of normal and cancerous pancreatic tissues have been measured within the range of 500-650 nm. Statistical significant differences between cancerous and normal tissues have been obtained at 550 nm and 630 nm for absorption coefficients. On the other hand; there were no statistical difference found for scattering coefficients at any wavelength.

Quantitative analysis of rectal cancer by spectral domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Zhang, Q. Q.; Wu, X. J.; Tang, T.; Zhu, S. W.; Yao, Q.; Gao, Bruce Z.; Yuan, X. C.

2012-08-01

To quantify OCT images of rectal tissue for clinic diagnosis, the scattering coefficient of the tissue is extracted by curve fitting the OCT signals to a confocal single model. A total of 1000 measurements (half and half of normal and malignant tissues) were obtained from 16 recta. The normal rectal tissue has a larger scattering coefficient ranging from 1.09 to 5.41 mm-1 with a mean value of 2.29 mm-1 (std:±0.32), while the malignant group shows lower scattering property and the values ranging from 0.25 to 2.69 mm-1 with a mean value of 1.41 mm-1 (std:±0.18). The peri-cancer of recta has also been investigated to distinguish the difference between normal and malignant rectal tissue. The results demonstrate that the quantitative analysis of the rectal tissue can be used as a promising diagnostic criterion of early rectal cancer, which has great value for clinical medical applications.

Minimally invasive photopolymerization in intervertebral disc tissue cavities

NASA Astrophysics Data System (ADS)

Schmocker, Andreas M.; Khoushabi, Azadeh; Gantenbein-Ritter, Benjamin; Chan, Samantha; Bonél, Harald Marcel; Bourban, Pierre-Etienne; Mânson, Jan Anders; Schizas, Constantin; Pioletti, Dominique; Moser, Christophe

2014-03-01

Photopolymerized hydrogels are commonly used for a broad range of biomedical applications. As long as the polymer volume is accessible, gels can easily be hardened using light illumination. However, in clinics, especially for minimally invasive surgery, it becomes highly challenging to control photopolymerization. The ratios between polymerizationvolume and radiating-surface-area are several orders of magnitude higher than for ex-vivo settings. Also tissue scattering occurs and influences the reaction. We developed a Monte Carlo model for photopolymerization, which takes into account the solid/liquid phase changes, moving solid/liquid-boundaries and refraction on these boundaries as well as tissue scattering in arbitrarily designable tissue cavities. The model provides a tool to tailor both the light probe and the scattering/absorption properties of the photopolymer for applications such as medical implants or tissue replacements. Based on the simulations, we have previously shown that by adding scattering additives to the liquid monomer, the photopolymerized volume was considerably increased. In this study, we have used bovine intervertebral disc cavities, as a model for spinal degeneration, to study photopolymerization in-vitro. The cavity is created by enzyme digestion. Using a custom designed probe, hydrogels were injected and photopolymerized. Magnetic resonance imaging (MRI) and visual inspection tools were employed to investigate the successful photopolymerization outcomes. The results provide insights for the development of novel endoscopic light-scattering polymerization probes paving the way for a new generation of implantable hydrogels.

Linear attenuation coefficients of tissues from 1 keV to 150 keV

NASA Astrophysics Data System (ADS)

Böke, Aysun

2014-09-01

The linear attenuation coefficients and three interaction processes have been computed for liver, kidney, muscle, fat and for a range of x-ray energies from 1 keV to 150 keV. Molecular photoelectric absorption cross sections were calculated from atomic cross section data. Total coherent (Rayleigh) and incoherent (Compton) scattering cross sections were obtained by numerical integration over combinations of F2m(x) with the Thomson formula and Sm(x) with the Klein-Nishina formula, respectively. For the coherent (Rayleigh) scattering cross section calculations, molecular form factors were obtained from recent experimental data in the literature for values of x<1 Å-1 and from the relativistic modified atomic form factors for values of x≥1 Å-1. With the inclusion of molecular interference effects in the coherent (Rayleigh) scattering, more accurate knowledge of the scatter from these tissues will be provided. The number of elements involved in tissue composition is 5 for liver, 47 for kidney, 44 for muscle and 3 for fat. The results are compared with previously published experimental and theoretical linear attenuation coefficients. In general, good agreement is obtained. The molecular form factors and scattering functions and cross sections are incorporated into a Monte Carlo program. The energy distributions of x-ray photons scattered from tissues have been simulated and the results are presented.

Label-free multiphoton microscopy reveals altered tissue architecture in hippocampal sclerosis.

PubMed

Uckermann, Ortrud; Galli, Roberta; Leupold, Susann; Coras, Roland; Meinhardt, Matthias; Hallmeyer-Elgner, Susanne; Mayer, Thomas; Storch, Alexander; Schackert, Gabriele; Koch, Edmund; Blümcke, Ingmar; Steiner, Gerald; Kirsch, Matthias

2017-01-01

The properties and structure of tissue can be visualized without labeling or preparation by multiphoton microscopy combining coherent anti-Stokes Raman scattering (CARS), addressing lipid content, second harmonic generation (SHG) showing collagen, and two-photon excited fluorescence (TPEF) of endogenous fluorophores. We compared samples of sclerotic and nonsclerotic human hippocampus to detect pathologic changes in the brain of patients with pharmacoresistant temporomesial epilepsy (n = 15). Multiphoton microscopy of cryosections and bulk tissue revealed hippocampal layering and micromorphologic details in accordance with reference histology: CARS displayed white and gray matter layering and allowed the assessment of axonal myelin. SHG visualized blood vessels based on adventitial collagen. In addition, corpora amylacea (CoA) were found to be SHG-active. Pyramidal cell bodies were characterized by intense cytoplasmic endogenous TPEF. Furthermore, diffuse TPEF around blood vessels was observed that co-localized with positive albumin immunohistochemistry and might indicate degeneration-associated vascular leakage. We present a label-free and fast optical approach that analyzes pathologic aspects of HS. Hippocampal layering, loss of pyramidal cells, and presence of CoA indicative of sclerosis are visualized. Label-free multiphoton microscopy has the potential to extend the histopathologic armamentarium for ex vivo assessment of changes of the hippocampal formation on fresh tissue and prospectively in vivo. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Automatic brain tissue segmentation based on graph filter.

PubMed

Kong, Youyong; Chen, Xiaopeng; Wu, Jiasong; Zhang, Pinzheng; Chen, Yang; Shu, Huazhong

2018-05-09

Accurate segmentation of brain tissues from magnetic resonance imaging (MRI) is of significant importance in clinical applications and neuroscience research. Accurate segmentation is challenging due to the tissue heterogeneity, which is caused by noise, bias filed and partial volume effects. To overcome this limitation, this paper presents a novel algorithm for brain tissue segmentation based on supervoxel and graph filter. Firstly, an effective supervoxel method is employed to generate effective supervoxels for the 3D MRI image. Secondly, the supervoxels are classified into different types of tissues based on filtering of graph signals. The performance is evaluated on the BrainWeb 18 dataset and the Internet Brain Segmentation Repository (IBSR) 18 dataset. The proposed method achieves mean dice similarity coefficient (DSC) of 0.94, 0.92 and 0.90 for the segmentation of white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF) for BrainWeb 18 dataset, and mean DSC of 0.85, 0.87 and 0.57 for the segmentation of WM, GM and CSF for IBSR18 dataset. The proposed approach can well discriminate different types of brain tissues from the brain MRI image, which has high potential to be applied for clinical applications.

Computational analysis of transcranial magnetic stimulation in the presence of deep brain stimulation probes

NASA Astrophysics Data System (ADS)

Syeda, F.; Holloway, K.; El-Gendy, A. A.; Hadimani, R. L.

2017-05-01

Transcranial Magnetic Stimulation is an emerging non-invasive treatment for depression, Parkinson's disease, and a variety of other neurological disorders. Many Parkinson's patients receive the treatment known as Deep Brain Stimulation, but often require additional therapy for speech and swallowing impairment. Transcranial Magnetic Stimulation has been explored as a possible treatment by stimulating the mouth motor area of the brain. We have calculated induced electric field, magnetic field, and temperature distributions in the brain using finite element analysis and anatomically realistic heterogeneous head models fitted with Deep Brain Stimulation leads. A Figure of 8 coil, current of 5000 A, and frequency of 2.5 kHz are used as simulation parameters. Results suggest that Deep Brain Stimulation leads cause surrounding tissues to experience slightly increased E-field (Δ Emax =30 V/m), but not exceeding the nominal values induced in brain tissue by Transcranial Magnetic Stimulation without leads (215 V/m). The maximum temperature in the brain tissues surrounding leads did not change significantly from the normal human body temperature of 37 °C. Therefore, we ascertain that Transcranial Magnetic Stimulation in the mouth motor area may stimulate brain tissue surrounding Deep Brain Stimulation leads, but will not cause tissue damage.

Long-Term Implanted cOFM Probe Causes Minimal Tissue Reaction in the Brain

PubMed Central

Hochmeister, Sonja; Asslaber, Martin; Kroath, Thomas; Pieber, Thomas R.; Sinner, Frank

2014-01-01

This study investigated the histological tissue reaction to long-term implanted cerebral open flow microperfusion (cOFM) probes in the frontal lobe of the rat brain. Most probe-based cerebral fluid sampling techniques are limited in application time due to the formation of a glial scar that hinders substance exchange between brain tissue and the probe. A glial scar not only functions as a diffusion barrier but also alters metabolism and signaling in extracellular brain fluid. cOFM is a recently developed probe-based technique to continuously sample extracellular brain fluid with an intact blood-brain barrier. After probe implantation, a 2 week healing period is needed for blood-brain barrier reestablishment. Therefore, cOFM probes need to stay in place and functional for at least 15 days after implantation to ensure functionality. Probe design and probe materials are optimized to evoke minimal tissue reaction even after a long implantation period. Qualitative and quantitative histological tissue analysis revealed no continuous glial scar formation around the cOFM probe 30 days after implantation and only a minor tissue reaction regardless of perfusion of the probe. PMID:24621608

HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

PubMed

Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

2011-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

Dental optical coherence domain reflectometry explorer

DOEpatents

Everett, Matthew J.; Colston, Jr., Billy W.; Sathyam, Ujwal S.; Da Silva, Luiz B.

2001-01-01

A hand-held, fiber optic based dental device with optical coherence domain reflectometry (OCDR) sensing capabilities provides a profile of optical scattering as a function of depth in the tissue at the point where the tip of the dental explorer touches the tissue. This system provides information on the internal structure of the dental tissue, which is then used to detect caries and periodontal disease. A series of profiles of optical scattering or tissue microstructure are generated by moving the explorer across the tooth or other tissue. The profiles are combined to form a cross-sectional, or optical coherence tomography (OCT), image.

Effect of Ginkgo biloba extract on apoptosis of brain tissues in rats with acute cerebral infarction and related gene expression.

PubMed

Wu, C; Zhao, X; Zhang, X; Liu, S; Zhao, H; Chen, Y

2015-06-11

We investigated the effect of Ginkgo biloba extract on apoptosis of brain tissues in rats with acute cerebral infarction and apoptosis-related gene expression. Rat models of acute cerebral infarction were constructed using the suture method, and randomly divided into the control group, model, and treatment groups. In the treatment group, 4 mg/kg G. biloba extract was intravenously injected into the rat tail vein. Phosphate-buffered saline solution was injected in the model group. Seventy-two hours after treatment, rats were euthanized, and brain tissues were removed to analyze the changes in caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) mRNA and protein levels, and variation in brain tissue cells' apoptosis indices was measured. Compared with the control group, the model and treatment groups showed significantly upregulated caspase-3, Bcl-2, and Bax mRNA and protein levels in brain tissues, but remarkably downregulated Bcl-2 mRNA and protein levels (P < 0.05). After treatment, in treatment group brain tissues, caspase-3 and Bax mRNA and protein levels were significantly lower than those in the model group, while Bcl-2 mRNA and protein levels were higher than that in the model group (P < 0.05). The model and treatment groups showed increased cell apoptosis indices of brain tissues compared to the control group; after treatment, the apoptosis index in the treatment group was significantly downregulated compared with that in the model group (P < 0.05). In conclusion, G. biloba extract significantly reduced apoptosis in rat brain tissue cells with acute cerebral infarction and thus protected brain tissues.

Roadmap on neurophotonics

NASA Astrophysics Data System (ADS)

Cho, Yong Ku; Zheng, Guoan; Augustine, George J.; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S.; Vellekoop, Ivo M.; Booth, Martin J.; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2016-09-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken.

Roadmap on neurophotonics

PubMed Central

Cho, Yong Ku; Zheng, Guoan; Augustine, George J; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S; Vellekoop, Ivo M; Booth, Martin J; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2017-01-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken. PMID:28386392

Quantitative Evaluation of 2 Scatter-Correction Techniques for 18F-FDG Brain PET/MRI in Regard to MR-Based Attenuation Correction.

PubMed

Teuho, Jarmo; Saunavaara, Virva; Tolvanen, Tuula; Tuokkola, Terhi; Karlsson, Antti; Tuisku, Jouni; Teräs, Mika

2017-10-01

In PET, corrections for photon scatter and attenuation are essential for visual and quantitative consistency. MR attenuation correction (MRAC) is generally conducted by image segmentation and assignment of discrete attenuation coefficients, which offer limited accuracy compared with CT attenuation correction. Potential inaccuracies in MRAC may affect scatter correction, because the attenuation image (μ-map) is used in single scatter simulation (SSS) to calculate the scatter estimate. We assessed the impact of MRAC to scatter correction using 2 scatter-correction techniques and 3 μ-maps for MRAC. Methods: The tail-fitted SSS (TF-SSS) and a Monte Carlo-based single scatter simulation (MC-SSS) algorithm implementations on the Philips Ingenuity TF PET/MR were used with 1 CT-based and 2 MR-based μ-maps. Data from 7 subjects were used in the clinical evaluation, and a phantom study using an anatomic brain phantom was conducted. Scatter-correction sinograms were evaluated for each scatter correction method and μ-map. Absolute image quantification was investigated with the phantom data. Quantitative assessment of PET images was performed by volume-of-interest and ratio image analysis. Results: MRAC did not result in large differences in scatter algorithm performance, especially with TF-SSS. Scatter sinograms and scatter fractions did not reveal large differences regardless of the μ-map used. TF-SSS showed slightly higher absolute quantification. The differences in volume-of-interest analysis between TF-SSS and MC-SSS were 3% at maximum in the phantom and 4% in the patient study. Both algorithms showed excellent correlation with each other with no visual differences between PET images. MC-SSS showed a slight dependency on the μ-map used, with a difference of 2% on average and 4% at maximum when a μ-map without bone was used. Conclusion: The effect of different MR-based μ-maps on the performance of scatter correction was minimal in non-time-of-flight 18 F-FDG PET/MR brain imaging. The SSS algorithm was not affected significantly by MRAC. The performance of the MC-SSS algorithm is comparable but not superior to TF-SSS, warranting further investigations of algorithm optimization and performance with different radiotracers and time-of-flight imaging. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

High-resolution imaging of the large non-human primate brain using microPET: a feasibility study

NASA Astrophysics Data System (ADS)

Naidoo-Variawa, S.; Hey-Cunningham, A. J.; Lehnert, W.; Kench, P. L.; Kassiou, M.; Banati, R.; Meikle, S. R.

2007-11-01

The neuroanatomy and physiology of the baboon brain closely resembles that of the human brain and is well suited for evaluating promising new radioligands in non-human primates by PET and SPECT prior to their use in humans. These studies are commonly performed on clinical scanners with 5 mm spatial resolution at best, resulting in sub-optimal images for quantitative analysis. This study assessed the feasibility of using a microPET animal scanner to image the brains of large non-human primates, i.e. papio hamadryas (baboon) at high resolution. Factors affecting image accuracy, including scatter, attenuation and spatial resolution, were measured under conditions approximating a baboon brain and using different reconstruction strategies. Scatter fraction measured 32% at the centre of a 10 cm diameter phantom. Scatter correction increased image contrast by up to 21% but reduced the signal-to-noise ratio. Volume resolution was superior and more uniform using maximum a posteriori (MAP) reconstructed images (3.2-3.6 mm3 FWHM from centre to 4 cm offset) compared to both 3D ordered subsets expectation maximization (OSEM) (5.6-8.3 mm3) and 3D reprojection (3DRP) (5.9-9.1 mm3). A pilot 18F-2-fluoro-2-deoxy-d-glucose ([18F]FDG) scan was performed on a healthy female adult baboon. The pilot study demonstrated the ability to adequately resolve cortical and sub-cortical grey matter structures in the baboon brain and improved contrast when images were corrected for attenuation and scatter and reconstructed by MAP. We conclude that high resolution imaging of the baboon brain with microPET is feasible with appropriate choices of reconstruction strategy and corrections for degrading physical effects. Further work to develop suitable correction algorithms for high-resolution large primate imaging is warranted.

Estimation of elasticity map of soft biological tissue mimicking phantom using laser speckle contrast analysis

NASA Astrophysics Data System (ADS)

Suheshkumar Singh, M.; Rajan, K.; Vasu, R. M.

2011-05-01

Scattering of coherent light from scattering particles causes phase shift to the scattered light. The interference of unscattered and scattered light causes the formation of speckles. When the scattering particles, under the influence of an ultrasound (US) pressure wave, vibrate, the phase shift fluctuates, thereby causing fluctuation in speckle intensity. We use the laser speckle contrast analysis (LSCA) to reconstruct a map of the elastic property (Young's modulus) of soft tissue-mimicking phantom. The displacement of the scatters is inversely related to the Young's modulus of the medium. The elastic properties of soft biological tissues vary, many fold with malignancy. The experimental results show that laser speckle contrast (LSC) is very sensitive to the pathological changes in a soft tissue medium. The experiments are carried out on a phantom with two cylindrical inclusions of sizes 6mm in diameter, separated by 8mm between them. Three samples are made. One inclusion has Young's modulus E of 40kPa. The second inclusion has either a Young's modulus E of 20kPa, or scattering coefficient of μs'=3.00mm-1 or absorption coefficient of μa=0.03mm-1. The optical absorption (μa), reduced scattering (μs') coefficient, and the Young's modulus of the background are μa=0.01mm-1, μs'=1.00mm-1 and 12kPa, respectively. The experiments are carried out on all three phantoms. On a phantom with two inclusions of Young's modulus of 20 and 40kPa, the measured relative speckle image contrasts are 36.55% and 63.72%, respectively. Experiments are repeated on phantoms with inclusions of μa=0.03mm-1, E =40kPa and μs'=3.00mm-1. The results show that it is possible to detect inclusions with contrasts in optical absorption, optical scattering, and Young's modulus. Studies of the variation of laser speckle contrast with ultrasound driving force for various values of μa, μs', and Young's modulus of the tissue mimicking medium are also carried out.

Acoustic radiation force due to arbitrary incident fields on spherical particles in soft tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Treweek, Benjamin C., E-mail: btreweek@utexas.edu; Ilinskii, Yurii A.; Zabolotskaya, Evgenia A.

Acoustic radiation force is of interest in a wide variety of biomedical applications ranging from tissue characterization (e.g. elastography) to tissue treatment (e.g. high intensity focused ultrasound, kidney stone fragment removal). As tissue mechanical properties are reliable indicators of tissue health, the former is the focus of the present contribution. This is accomplished through an investigation of the acoustic radiation force on a spherical scatterer embedded in tissue. Properties of both the scatterer and the surrounding tissue are important in determining the magnitude and the direction of the force. As these properties vary, the force computation shows changes in magnitudemore » and direction, which may enable more accurate noninvasive determination of tissue properties.« less

Acoustic radiation force due to arbitrary incident fields on spherical particles in soft tissue

NASA Astrophysics Data System (ADS)

Treweek, Benjamin C.; Ilinskii, Yurii A.; Zabolotskaya, Evgenia A.; Hamilton, Mark F.

2015-10-01

Acoustic radiation force is of interest in a wide variety of biomedical applications ranging from tissue characterization (e.g. elastography) to tissue treatment (e.g. high intensity focused ultrasound, kidney stone fragment removal). As tissue mechanical properties are reliable indicators of tissue health, the former is the focus of the present contribution. This is accomplished through an investigation of the acoustic radiation force on a spherical scatterer embedded in tissue. Properties of both the scatterer and the surrounding tissue are important in determining the magnitude and the direction of the force. As these properties vary, the force computation shows changes in magnitude and direction, which may enable more accurate noninvasive determination of tissue properties.

Laser induced heat source distribution in bio-tissues

NASA Astrophysics Data System (ADS)

Li, Xiaoxia; Fan, Shifu; Zhao, Youquan

2006-09-01

During numerical simulation of laser and tissue thermal interaction, the light fluence rate distribution should be formularized and constituted to the source term in the heat transfer equation. Usually the solution of light irradiative transport equation is given in extreme conditions such as full absorption (Lambert-Beer Law), full scattering (Lubelka-Munk theory), most scattering (Diffusion Approximation) et al. But in specific conditions, these solutions will induce different errors. The usually used Monte Carlo simulation (MCS) is more universal and exact but has difficulty to deal with dynamic parameter and fast simulation. Its area partition pattern has limits when applying FEM (finite element method) to solve the bio-heat transfer partial differential coefficient equation. Laser heat source plots of above methods showed much difference with MCS. In order to solve this problem, through analyzing different optical actions such as reflection, scattering and absorption on the laser induced heat generation in bio-tissue, a new attempt was made out which combined the modified beam broaden model and the diffusion approximation model. First the scattering coefficient was replaced by reduced scattering coefficient in the beam broaden model, which is more reasonable when scattering was treated as anisotropic scattering. Secondly the attenuation coefficient was replaced by effective attenuation coefficient in scattering dominating turbid bio-tissue. The computation results of the modified method were compared with Monte Carlo simulation and showed the model provided reasonable predictions of heat source term distribution than past methods. Such a research is useful for explaining the physical characteristics of heat source in the heat transfer equation, establishing effective photo-thermal model, and providing theory contrast for related laser medicine experiments.

Determination of optical coefficients of biological tissue from a single integrating-sphere

NASA Astrophysics Data System (ADS)

Zhang, Lianshun; Shi, Aijuan; Lu, Hongguang

2012-01-01

The detection of interactions between light and tissue can be used to characterize the optical properties of the tissue. The development is described of a method that determines optical coefficients of biological tissue from a single optical reflectance spectrum measured with an integrating-sphere. The experimental system incorporated a DH-2000 deuterium tungsten halogen light source, a USB4000-VIS-NIR miniature fiber optic spectrometer and an integrating-sphere. Fat emulsion and ink were used to mimic the scattering and absorbing properties of tissue in the tested sample. The measured optical reflectance spectrums with different scattering and absorbing properties were used to train a back-propagation neural network (BPNN). Then the neural network (BPNN) was used to determine the optical coefficients of biological tissue from a single optical reflectance spectrum measured with an integrating-sphere. Tests on tissue-simulation phantoms showed the relative errors of this technique to be 7% for the reduced scattering coefficient and 15% for the absorption coefficients. The optical properties of human skin were also measured in vivo.

Ultrasound modulation of bioluminescence generated inside a turbid medium

NASA Astrophysics Data System (ADS)

Ahmad, Junaid; Jayet, Baptiste; Hill, Philip J.; Mather, Melissa L.; Dehghani, Hamid; Morgan, Stephen P.

2017-03-01

In vivo bioluminescence imaging (BLI) has poor spatial resolution owing to strong light scattering by tissue, which also affects quantitative accuracy. This paper proposes a hybrid acousto-optic imaging platform that images bioluminescence modulated at ultrasound (US) frequency inside an optically scattering medium. This produces an US modulated light within the tissue that reduces the effects of light scattering and improves the spatial resolution. The system consists of a continuously excited 3.5 MHz US transducer applied to a tissue like phantom of known optical properties embedded with bio-or chemiluminescent sources that are used to mimic in vivo experiments. Scanning US over the turbid medium modulates the luminescent sources deep inside tissue at several US scan points. These modulated signals are recorded by a photomultiplier tube and lock-in detection to generate a 1D profile. Indeed, high frequency US enables small focal volume to improve spatial resolution, but this leads to lower signal-to-noise ratio. First experimental results show that US enables localization of a small luminescent source (around 2 mm wide) deep ( 20 mm) inside a tissue phantom having a scattering coefficient of 80 cm-1. Two sources separated by 10 mm could be resolved 20 mm inside a chicken breast.

Noninvasively Imaging Subcutaneous Tumor Xenograft by a Handheld Raman Detector, with the Assistance of an Optical Clearing Agent.

PubMed

Zhang, Yunfei; Liu, Haoran; Tang, Jiali; Li, Zhuoyun; Zhou, Xingyu; Zhang, Ren; Chen, Liang; Mao, Ying; Li, Cong

2017-05-31

A handheld Raman detector with operational convenience, high portability, and rapid acquisition rate has been applied in clinics for diagnostic purposes. However, the inherent weakness of Raman scattering and strong scattering of the turbid tissue restricts its utilization to superficial locations. To extend the applications of a handheld Raman detector to deep tissues, a gold nanostar-based surface-enhanced Raman scattering (SERS) nanoprobe with robust colloidal stability, a fingerprint-like spectrum, and extremely high sensitivity (5.0 fM) was developed. With the assistance of FPT, a multicomponent optical clearing agent (OCA) efficiently suppressing light scattering from the turbid dermal tissues, the handheld Raman detector noninvasively visualized the subcutaneous tumor xenograft with a high target-to-background ratio after intravenous injection of the gold nanostar-based SERS nanoprobe. To the best of our knowledge, this work is the first example to introduce the optical clearing technique in assisting SERS imaging in vivo. The combination of optical clearing technology and SERS is a promising strategy for the extension of the clinical applications of the handheld Raman detector from superficial tissues to subcutaneous or even deeper lesions that are usually "concealed" by the turbid dermal tissue.

Performance of a lookup table-based approach for measuring tissue optical properties with diffuse optical spectroscopy

NASA Astrophysics Data System (ADS)

Nichols, Brandon S.; Rajaram, Narasimhan; Tunnell, James W.

2012-05-01

Diffuse optical spectroscopy (DOS) provides a powerful tool for fast and noninvasive disease diagnosis. The ability to leverage DOS to accurately quantify tissue optical parameters hinges on the model used to estimate light-tissue interaction. We describe the accuracy of a lookup table (LUT)-based inverse model for measuring optical properties under different conditions relevant to biological tissue. The LUT is a matrix of reflectance values acquired experimentally from calibration standards of varying scattering and absorption properties. Because it is based on experimental values, the LUT inherently accounts for system response and probe geometry. We tested our approach in tissue phantoms containing multiple absorbers, different sizes of scatterers, and varying oxygen saturation of hemoglobin. The LUT-based model was able to extract scattering and absorption properties under most conditions with errors of less than 5 percent. We demonstrate the validity of the lookup table over a range of source-detector separations from 0.25 to 1.48 mm. Finally, we describe the rapid fabrication of a lookup table using only six calibration standards. This optimized LUT was able to extract scattering and absorption properties with average RMS errors of 2.5 and 4 percent, respectively.

Identification of the boundary between normal brain tissue and ischemia region using two-photon excitation fluorescence microscopy

NASA Astrophysics Data System (ADS)

Du, Huiping; Wang, Shu; Wang, Xingfu; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

2016-10-01

Ischemic stroke is one of the common neurological diseases, and it is becoming the leading causes of death and permanent disability around the world. Early and accurate identification of the potentially salvageable boundary region of ischemia brain tissues may enable selection of the most appropriate candidates for early stroke therapies. In this work, TPEF microscopy was used to image the microstructures of normal brain tissues, ischemia regions and the boundary region between normal and ischemia brain tissues. The ischemia brain tissues from Sprague-Dawley (SD) rats were subjected to 6 hours of middle cerebral artery occlusion (MCAO). Our study demonstrates that TPEF microscopy has the ability to not only reveal the morphological changes of the neurons but also identify the boundary between normal brain tissue and ischemia region, which correspond well to the hematoxylin and eosin (H and E) stained images. With the development of miniaturized TPEF microscope imaging devices, TPEF microscopy can be developed into an effectively diagnostic and monitoring tool for cerebral ischemia.

EBG Based Microstrip Patch Antenna for Brain Tumor Detection via Scattering Parameters in Microwave Imaging System.

PubMed

Inum, Reefat; Rana, Md Masud; Shushama, Kamrun Nahar; Quader, Md Anwarul

2018-01-01

A microwave brain imaging system model is envisaged to detect and visualize tumor inside the human brain. A compact and efficient microstrip patch antenna is used in the imaging technique to transmit equivalent signal and receive backscattering signal from the stratified human head model. Electromagnetic band gap (EBG) structure is incorporated on the antenna ground plane to enhance the performance. Rectangular and circular EBG structures are proposed to investigate the antenna performance. Incorporation of circular EBG on the antenna ground plane provides an improvement of 22.77% in return loss, 5.84% in impedance bandwidth, and 16.53% in antenna gain with respect to the patch antenna with rectangular EBG. The simulation results obtained from CST are compared to those obtained from HFSS to validate the design. Specific absorption rate (SAR) of the modeled head tissue for the proposed antenna is determined. Different SAR values are compared with the established standard SAR limit to provide a safety regulation of the imaging system. A monostatic radar-based confocal microwave imaging algorithm is applied to generate the image of tumor inside a six-layer human head phantom model. S -parameter signals obtained from circular EBG loaded patch antenna in different scanning modes are utilized in the imaging algorithm to effectively produce a high-resolution image which reliably indicates the presence of tumor inside human brain.

EBG Based Microstrip Patch Antenna for Brain Tumor Detection via Scattering Parameters in Microwave Imaging System

PubMed Central

Rana, Md. Masud; Shushama, Kamrun Nahar; Quader, Md. Anwarul

2018-01-01

A microwave brain imaging system model is envisaged to detect and visualize tumor inside the human brain. A compact and efficient microstrip patch antenna is used in the imaging technique to transmit equivalent signal and receive backscattering signal from the stratified human head model. Electromagnetic band gap (EBG) structure is incorporated on the antenna ground plane to enhance the performance. Rectangular and circular EBG structures are proposed to investigate the antenna performance. Incorporation of circular EBG on the antenna ground plane provides an improvement of 22.77% in return loss, 5.84% in impedance bandwidth, and 16.53% in antenna gain with respect to the patch antenna with rectangular EBG. The simulation results obtained from CST are compared to those obtained from HFSS to validate the design. Specific absorption rate (SAR) of the modeled head tissue for the proposed antenna is determined. Different SAR values are compared with the established standard SAR limit to provide a safety regulation of the imaging system. A monostatic radar-based confocal microwave imaging algorithm is applied to generate the image of tumor inside a six-layer human head phantom model. S-parameter signals obtained from circular EBG loaded patch antenna in different scanning modes are utilized in the imaging algorithm to effectively produce a high-resolution image which reliably indicates the presence of tumor inside human brain. PMID:29623087

Large area, label-free imaging of extracellular matrix using telecentricity

NASA Astrophysics Data System (ADS)

Visbal Onufrak, Michelle A.; Konger, Raymond L.; Kim, Young L.

2017-02-01

Subtle alterations in stromal tissue structures and organizations within the extracellular matrix (ECM) have been observed in several types of tissue abnormalities, including early skin cancer and wounds. Current microscopic imaging methods often lack the ability to accurately determine the extent of malignancy over a large area, due to their limited field of view. In this research we focus on the development of simple mesoscopic (i.e. between microscopic and macroscopic) biomedical imaging device for non-invasive assessment of ECM alterations over a large, heterogeneous area. In our technology development, a telecentric lens, commonly used in machine vision systems but rarely used in biomedical imaging, serves as a key platform to visualize alterations in tissue microenvironments in a label-free manner over a clinically relevant area. In general, telecentric imaging represents a simple, alternative method for reducing unwanted scattering or diffuse light caused by the highly anisotropic scattering properties of biological tissue. In particular, under telecentric imaging the light intensity backscattered from biological tissue is mainly sensitive to the scattering anisotropy factor, possibly associated with the ECM. We demonstrate the inherent advantages of combining telecentric lens systems with hyperspectral imaging for providing optical information of tissue scattering in biological tissue of murine models, as well as light absorption of hemoglobin in blood vessel tissue phantoms. Thus, we envision that telecentric imaging could potentially serve for simple site-specific, tissue-based assessment of stromal alterations over a clinically relevant field of view in a label-free manner, for studying diseases associated with disruption of homeostasis in ECM.

Comparative study of the optical properties of colon mucosa and colon precancerous polyps between 400 and 1000 nm

NASA Astrophysics Data System (ADS)

Carvalho, Sónia; Gueiral, Nuno; Nogueira, Elisabete; Henrique, Rui; Oliveira, Luís.; Tuchin, Valery V.

2017-03-01

Optical properties of biological tissues are unique and may be used for tissue identification, tissue discrimination or even to identify pathologies. Early stage colorectal cancer evolves from adenomatous polyps that arise in the inner layer of the colorectal tube - the mucosa. The identification of different optical properties between healthy and pathological colorectal tissues might be used to identify different tissue components and to develop an early stage diagnosis method using optical technologies. Since most of the biomedical optics techniques use light within the visible and near infrared wavelength ranges, we used the inverse adding-doubling method to make a fast estimation of the optical properties of colorectal mucosa and early stage adenocarcinoma between 400 and 1000 nm. The estimated wavelength dependencies have provided information about higher lipid content in healthy mucosa and higher blood content in pathological tissue. Such data has also indicated that the wavelength dependence of the scattering coefficient for healthy mucosa is dominated by Rayleigh scattering and for pathological mucosa it is dominated by Mie scattering. Such difference indicates smaller scatterer size in healthy mucosa tissue. Such information can now be used to develop new diagnosis or treatment methods for early cancer detection or removal. One possibility is to use optical clearing technique to improve tissue transparency and create localized and temporary tissue dehydration for image contrast improvement during diagnosis or polyp laser removal. Such techniques can now be developed based on the different results that we have found for healthy and pathological colorectal mucosa.

Ultrasound wave propagation in tissue and scattering from microbubbles for echo particle image velocimetry technique.

PubMed

Mukdadi, Osama; Shandas, Robin

2004-01-01

Nonlinear wave propagation in tissue can be employed for tissue harmonic imaging, ultrasound surgery, and more effective tissue ablation for high intensity focused ultrasound (HIFU). Wave propagation in soft tissue and scattering from microbubbles (ultrasound contrast agents) are modeled to improve detectability, signal-to-noise ratio, and contrast harmonic imaging used for echo particle image velocimetry (Echo-PIV) technique. The wave motion in nonlinear material (tissue) is studied using KZK-type parabolic evolution equation. This model considers ultrasound beam diffraction, attenuation, and tissue nonlinearity. Time-domain numerical model is based on that originally developed by Lee and Hamilton [J. Acoust. Soc. Am 97:906-917 (1995)] for axi-symmetric acoustic field. The initial acoustic waveform emitted from the transducer is assumed to be a broadband wave modulated by Gaussian envelope. Scattering from microbubbles seeded in the blood stream is characterized. Hence, we compute the pressure field impinges the wall of a coated microbubble; the dynamics of oscillating microbubble can be modeled using Rayleigh-Plesset-type equation. Here, the continuity and the radial-momentum equation of encapsulated microbubbles are used to account for the lipid layer surrounding the microbubble. Numerical results show the effects of tissue and microbubble nonlinearities on the propagating pressure wave field. These nonlinearities have a strong influence on the waveform distortion and harmonic generation of the propagating and scattering waves. Results also show that microbubbles have stronger nonlinearity than tissue, and thus improves S/N ratio. These theoretical predictions of wave phenomena provide further understanding of biomedical imaging technique and provide better system design.

Time domain diffuse optical spectroscopy: In vivo quantification of collagen in breast tissue

NASA Astrophysics Data System (ADS)

Taroni, Paola; Pifferi, Antonio; Quarto, Giovanna; Farina, Andrea; Ieva, Francesca; Paganoni, Anna Maria; Abbate, Francesca; Cassano, Enrico; Cubeddu, Rinaldo

2015-05-01

Time-resolved diffuse optical spectroscopy provides non-invasively the optical characterization of highly diffusive media, such as biological tissues. Light pulses are injected into the tissue and the effects of light propagation on re-emitted pulses are interpreted with the diffusion theory to assess simultaneously tissue absorption and reduced scattering coefficients. Performing spectral measurements, information on tissue composition and structure is derived applying the Beer law to the measured absorption and an empiric approximation to Mie theory to the reduced scattering. The absorption properties of collagen powder were preliminarily measured in the range of 600-1100 nm using a laboratory set-up for broadband time-resolved diffuse optical spectroscopy. Optical projection images were subsequently acquired in compressed breast geometry on 218 subjects, either healthy or bearing breast lesions, using a portable instrument for optical mammography that operates at 7 wavelengths selected in the range 635-1060 nm. For all subjects, tissue composition was estimated in terms of oxy- and deoxy-hemoglobin, water, lipids, and collagen. Information on tissue microscopic structure was also derived. Good correlation was obtained between mammographic breast density (a strong risk factor for breast cancer) and an optical index based on collagen content and scattering power (that accounts mostly for tissue collagen). Logistic regression applied to all optically derived parameters showed that subjects at high risk for developing breast cancer for their high breast density can effectively be identified based on collagen content and scattering parameters. Tissue composition assessed in breast lesions with a perturbative approach indicated that collagen and hemoglobin content are significantly higher in malignant lesions than in benign ones.

Full scattering profile of tissues with elliptical cross sections

NASA Astrophysics Data System (ADS)

Duadi, H.; Feder, I.; Fixler, D.

2018-02-01

Light reflectance and transmission from soft tissue has been utilized in noninvasive clinical measurement devices such as the photoplethysmograph (PPG) and reflectance pulse oximeter. Most methods of near infrared (NIR) spectroscopy focus on the volume reflectance from a semi-infinite sample, while very few measure transmission. However, since PPG and pulse oximetry are usually measured on tissue such as earlobe, fingertip, lip and pinched tissue, we propose examining the full scattering profile (FSP), which is the angular distribution of exiting photons. The FSP provides more comprehensive information when measuring from a cylindrical tissue. In our work we discovered a unique point, that we named the iso-pathlength (IPL) point, which is not dependent on changes in the reduced scattering coefficient (µs'). This IPL point was observed both in Monte Carlo (MC) simulation and in experimental tissue mimicking phantoms. The angle corresponding to this IPL point depends only on the tissue geometry. In the case of cylindrical tissues this point linearly depends on the tissue diameter. Since the target tissues for clinically physiological measuring are not a perfect cylinder, in this work we will examine how the change in the tissue cross section geometry influences the FSP and the IPL point. We used a MC simulation to compare a circular to an elliptic tissue cross section. The IPL point can serve as a self-calibration point for optical tissue measurements such as NIR spectroscopy, PPG and pulse oximetery.

Photoacoustic tomography based on the Green's function retrieval with ultrasound interferometry for sample partially behind an acoustically scattering layer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yin, Jie; Department of Automation, Nanjing Polytechnic Institute, 210048 Nanjing; Tao, Chao, E-mail: taochao@nju.edu.cn

2015-06-08

Acoustically inhomogeneous mediums with multiple scattering are often the nightmare of photoacoustic tomography. In order to break this limitation, a photoacoustic tomography scheme combining ultrasound interferometry and time reversal is proposed to achieve images in acoustically scattering medium. An ultrasound interferometry is developed to determine the unknown Green's function of strong scattering tissue. Using the determined Greens' function, a time-reversal process is carried out to restore images behind an acoustically inhomogeneous layer from the scattering photoacoustic signals. This method effectively decreases the false contrast, noise, and position deviation of images induced by the multiple scattering. Phantom experiment is carried outmore » to validate the method. Therefore, the proposed method could have potential value in extending the biomedical applications of photoacoustic tomography in acoustically inhomogeneous tissue.« less

Postmortem changes in the neuroanatomical characteristics of the primate brain: the hippocampal formation

PubMed Central

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L.; Amaral, David G.

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused, or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger, as compared to perfusion-fixed tissue. Non-phosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well-stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences. PMID:18972553

Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.

PubMed

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L; Amaral, David G

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences.

Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child.

PubMed

Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

2015-01-01

Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters.

4D (x-y-z-t) imaging of thick biological samples by means of Two-Photon inverted Selective Plane Illumination Microscopy (2PE-iSPIM)

PubMed Central

Lavagnino, Zeno; Sancataldo, Giuseppe; d’Amora, Marta; Follert, Philipp; De Pietri Tonelli, Davide; Diaspro, Alberto; Cella Zanacchi, Francesca

2016-01-01

In the last decade light sheet fluorescence microscopy techniques, such as selective plane illumination microscopy (SPIM), has become a well established method for developmental biology. However, conventional SPIM architectures hardly permit imaging of certain tissues since the common sample mounting procedure, based on gel embedding, could interfere with the sample morphology. In this work we propose an inverted selective plane microscopy system (iSPIM), based on non-linear excitation, suitable for 3D tissue imaging. First, the iSPIM architecture provides flexibility on the sample mounting, getting rid of the gel-based mounting typical of conventional SPIM, permitting 3D imaging of hippocampal slices from mouse brain. Moreover, all the advantages brought by two photon excitation (2PE) in terms of reduction of scattering effects and contrast improvement are exploited, demonstrating an improved image quality and contrast compared to single photon excitation. The system proposed represents an optimal platform for tissue imaging and it smooths the way to the applicability of light sheet microscopy to a wider range of samples including those that have to be mounted on non-transparent surfaces. PMID:27033347

Fundamental study for scattering suppression in biological tissue using digital phase-conjugate light with intensity modulation

NASA Astrophysics Data System (ADS)

Toda, Sogo; Kato, Yuji; Kudo, Nobuki; Shimizu, Koichi

2017-04-01

For transillumination imaging of an animal body, we have attempted to suppress the scattering effect in a turbid medium. It is possible to restore the optical image before scattering using phase-conjugate light. We examined the effect of intensity information as well as the phase information for the restoration of the original light distribution. In an experimental analysis using animal tissue, the contributions of the phase- and the intensity-information to the image restoration through turbid medium were demonstrated.

Computing the scatter component of mammographic images.

PubMed

Highnam, R P; Brady, J M; Shepstone, B J

1994-01-01

The authors build upon a technical report (Tech. Report OUEL 2009/93, Engng. Sci., Oxford Uni., Oxford, UK, 1993) in which they proposed a model of the mammographic imaging process for which scattered radiation is a key degrading factor. Here, the authors propose a way of estimating the scatter component of the signal at any pixel within a mammographic image, and they use this estimate for model-based image enhancement. The first step is to extend the authors' previous model to divide breast tissue into "interesting" (fibrous/glandular/cancerous) tissue and fat. The scatter model is then based on the idea that the amount of scattered radiation reaching a point is related to the energy imparted to the surrounding neighbourhood. This complex relationship is approximated using published empirical data, and it varies with the size of the breast being imaged. The approximation is further complicated by needing to take account of extra-focal radiation and breast edge effects. The approximation takes the form of a weighting mask which is convolved with the total signal (primary and scatter) to give a value which is input to a "scatter function", approximated using three reference cases, and which returns a scatter estimate. Given a scatter estimate, the more important primary component can be calculated and used to create an image recognizable by a radiologist. The images resulting from this process are clearly enhanced, and model verification tests based on an estimate of the thickness of interesting tissue present proved to be very successful. A good scatter model opens the was for further processing to remove the effects of other degrading factors, such as beam hardening.

Investigating backward scattered second harmonic generation from various mouse collagen tissues

NASA Astrophysics Data System (ADS)

Shen, Mengzhe; Tian, Yunxian; Chong, Shau Poh; Zhao, Jianhua; Zeng, Haishan; Tang, Shuo

2014-02-01

A confocal multiphoton microscopy system with various detection pinholes was used to differentiate backward scattered second harmonic generation (BS-SHG) from backward generated SHG (BG-SHG) based on the fact that BS-SHG is more scattered and therefore has a much bigger spot size than BG-SHG. BS-SHG is quantified from two types of mouse tissues, such as Achilles tendon, and skin, and at various focal depths. It is found that the BS-SHG contributes less to the total backward SHG for the skin than Achilles tendon with thicknesses of around three hundred micrometers. For tissue with larger F/B intensity ratio such as Achilles tendon, increasing the tissue thickness reduces it tremendously. However, for tissue with smaller F/B intensity ratio, tissue thickness increment does not alter it significantly. In addition, larger F/B intensity ratio might be related with a greater scattering coefficient from our Achilles tendon and skin comparison. When the focal point is moved deeper into tissue, the contribution of BS-SHG is found to decrease due to a reduced pass length of the forward propagated photons. On the contrary, when the tissue thickness increases, the contribution of the BS-SHG is increased. These observations for thicker skin tissues are related with our F/B intensity ratio measurement for thin mouse skin sample in terms of that the magnitude of backward generated SHG are dominant among the total backward SHG in mouse skin tissue. Considering the phase mismatching condition in the forward and backward directions, these results may indicate that quasi-phase matching originating from the regular structure of collagen could help with reducing the phase mismatch especially in the backward direction.

Multimodality Instrument for Tissue Characterization

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

2000-01-01

A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip is discussed. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network, program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration.

Scattering and absorption control in biocompatible fibers towards equalized photobiomodulation.

PubMed

George, J; Haghshenas, H; d'Hemecourt, D; Zhu, W; Zhang, L; Sorger, V

2017-03-01

Transparent tissue scaffolds enable illumination of growing tissue to accelerate cell proliferation and improve other cell functions through photobiomodulation. The biphasic dose response of cells exposed to photobiomodulating light dictates that the illumination be evenly distributed across the scaffold such that the cells are neither under nor over exposed to light. However, equalized illumination has not been sufficiently addressed. Here we analyze and experimentally demonstrate spatially equalizing illumination by three methods, namely: engineered surface scattering, reflection by a gold mirror, and traveling-waves in a ring mesh. Our results show that nearly equalized illumination is achievable by controlling the light scattering-to-loss ratio. This demonstration furthers opportunities for dose-optimized photobiomodulation in tissue regeneration.

The Importance of Brain Banks for Molecular Neuropathological Research: The New South Wales Tissue Resource Centre Experience

PubMed Central

Dedova, Irina; Harding, Antony; Sheedy, Donna; Garrick, Therese; Sundqvist, Nina; Hunt, Clare; Gillies, Juliette; Harper, Clive G.

2009-01-01

New developments in molecular neuropathology have evoked increased demands for postmortem human brain tissue. The New South Wales Tissue Resource Centre (TRC) at The University of Sydney has grown from a small tissue collection into one of the leading international brain banking facilities, which operates with best practice and quality control protocols. The focus of this tissue collection is on schizophrenia and allied disorders, alcohol use disorders and controls. This review highlights changes in TRC operational procedures dictated by modern neuroscience, and provides examples of applications of modern molecular techniques to study the neuropathogenesis of many different brain disorders. PMID:19333451

Different modes of herpes simplex virus type 1 spread in brain and skin tissues.

PubMed

Tsalenchuck, Yael; Tzur, Tomer; Steiner, Israel; Panet, Amos

2014-02-01

Herpes simplex virus type 1 (HSV-1) initially infects the skin and subsequently spreads to the nervous system. To investigate and compare HSV-1 mode of propagation in the two clinically relevant tissues, we have established ex vivo infection models, using native tissues of mouse and human skin, as well as mouse brain, maintained in organ cultures. HSV-1, which is naturally restricted to the human, infects and spreads in the mouse and human skin tissues in a similar fashion, thus validating the mouse model. The spread of HSV-1 in the skin was concentric to form typical plaques of limited size, predominantly of cytopathic cells. By contrast, HSV-1 spread in the brain tissue was directed along specific neuronal networks with no apparent cytopathic effect. Two additional differences were noted following infection of the skin and brain tissues. First, only a negligible amount of extracellular progeny virus was produced of the infected brain tissues, while substantial quantity of infectious progeny virus was released to the media of the infected skin. Second, antibodies against HSV-1, added following the infection, effectively restricted viral spread in the skin but have no effect on viral spread in the brain tissue. Taken together, these results reveal that HSV-1 spread within the brain tissue mostly by direct transfer from cell to cell, while in the skin the progeny extracellular virus predominates, thus facilitating the infection to new individuals.

TH-CD-207A-08: Simulated Real-Time Image Guidance for Lung SBRT Patients Using Scatter Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redler, G; Cifter, G; Templeton, A

2016-06-15

Purpose: To develop a comprehensive Monte Carlo-based model for the acquisition of scatter images of patient anatomy in real-time, during lung SBRT treatment. Methods: During SBRT treatment, images of patient anatomy can be acquired from scattered radiation. To rigorously examine the utility of scatter images for image guidance, a model is developed using MCNP code to simulate scatter images of phantoms and lung cancer patients. The model is validated by comparing experimental and simulated images of phantoms of different complexity. The differentiation between tissue types is investigated by imaging objects of known compositions (water, lung, and bone equivalent). A lungmore » tumor phantom, simulating materials and geometry encountered during lung SBRT treatments, is used to investigate image noise properties for various quantities of delivered radiation (monitor units(MU)). Patient scatter images are simulated using the validated simulation model. 4DCT patient data is converted to an MCNP input geometry accounting for different tissue composition and densities. Lung tumor phantom images acquired with decreasing imaging time (decreasing MU) are used to model the expected noise amplitude in patient scatter images, producing realistic simulated patient scatter images with varying temporal resolution. Results: Image intensity in simulated and experimental scatter images of tissue equivalent objects (water, lung, bone) match within the uncertainty (∼3%). Lung tumor phantom images agree as well. Specifically, tumor-to-lung contrast matches within the uncertainty. The addition of random noise approximating quantum noise in experimental images to simulated patient images shows that scatter images of lung tumors can provide images in as fast as 0.5 seconds with CNR∼2.7. Conclusions: A scatter imaging simulation model is developed and validated using experimental phantom scatter images. Following validation, lung cancer patient scatter images are simulated. These simulated patient images demonstrate the clinical utility of scatter imaging for real-time tumor tracking during lung SBRT.« less

Hyperspectral imaging solutions for brain tissue metabolic and hemodynamic monitoring: past, current and future developments

NASA Astrophysics Data System (ADS)

Giannoni, Luca; Lange, Frédéric; Tachtsidis, Ilias

2018-04-01

Hyperspectral imaging (HSI) technologies have been used extensively in medical research, targeting various biological phenomena and multiple tissue types. Their high spectral resolution over a wide range of wavelengths enables acquisition of spatial information corresponding to different light-interacting biological compounds. This review focuses on the application of HSI to monitor brain tissue metabolism and hemodynamics in life sciences. Different approaches involving HSI have been investigated to assess and quantify cerebral activity, mainly focusing on: (1) mapping tissue oxygen delivery through measurement of changes in oxygenated (HbO2) and deoxygenated (HHb) hemoglobin; and (2) the assessment of the cerebral metabolic rate of oxygen (CMRO2) to estimate oxygen consumption by brain tissue. Finally, we introduce future perspectives of HSI of brain metabolism, including its potential use for imaging optical signals from molecules directly involved in cellular energy production. HSI solutions can provide remarkable insight in understanding cerebral tissue metabolism and oxygenation, aiding investigation on brain tissue physiological processes.

A study on the antioxidant effect of Coriolus versicolor polysaccharide in rat brain tissues.

PubMed

Chen, Jiayu; Jin, Xiaoyan; Zhang, Liting; Yang, Linjun

2013-01-01

The objective of the study was to investigate the antioxidant effect of Chinese medicine Coriolus versicolor polysaccharide on brain tissue and its mechanism in rats. SOD, MDA and GSH-Px levels in rat brain tissues were determined with SD rats as the animal model. The results showed that Coriolus versicolor polysaccharide can reduce the lipid peroxidation level in brain tissues during exhaustive exercise in rats, and can accelerate the removal of free radicals. The study concluded that its antioxidant effect is relatively apparent.

Exploring infrared neural stimulation with multimodal nonlinear imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Adams, Wilson R.; Mahadevan-Jansen, Anita

2017-02-01

Infrared neural stimulation (INS) provides optical control of neural excitability using near to mid-infrared (mid-IR) light, which allows for spatially selective, artifact-free excitation without the introduction of exogenous agents or genetic modification. Although neural excitability is mediated by a transient temperature increase due to water absorption of IR energy, the molecular nature of IR excitability in neural tissue remains unknown. Current research suggests that transient changes in local tissue temperature give rise to a myriad of cellular responses that have been individually attributed to IR mediated excitability. To further elucidate the underlying biophysical mechanisms, we have begun work towards employing a novel multimodal nonlinear imaging platform to probe the molecular underpinnings of INS. Our imaging system performs coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS), two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG) and thermal imaging into a single platform that allows for unprecedented co-registration of thermal and biochemical information in real-time. Here, we present our work leveraging CARS and SRS in acute thalamocortical brain slice preparations. We observe the evolution of lipid and protein-specific Raman bands during INS and electrically evoked activity in real-time. Combined with two-photon fluorescence and second harmonic generation, we offer insight to cellular metabolism and membrane dynamics during INS. Thermal imaging allows for the coregistration of acquired biochemical information with temperature information. Our work previews the versatility and capabilities of coherent Raman imaging combined with multiphoton imaging to observe biophysical phenomena for neuroscience applications.

Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

2016-03-01

In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

Near-infrared spectral tomography integrated with digital breast tomosynthesis: Effects of tissue scattering on optical data acquisition design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michaelsen, Kelly; Krishnaswamy, Venkat; Pogue, Brian W.

2012-07-15

Purpose: Design optimization and phantom validation of an integrated digital breast tomosynthesis (DBT) and near-infrared spectral tomography (NIRST) system targeting improvement in sensitivity and specificity of breast cancer detection is presented. Factors affecting instrumentation design include minimization of cost, complexity, and examination time while maintaining high fidelity NIRST measurements with sufficient information to recover accurate optical property maps. Methods: Reconstructed DBT slices from eight patients with abnormal mammograms provided anatomical information for the NIRST simulations. A limited frequency domain (FD) and extensive continuous wave (CW) NIRST system was modeled. The FD components provided tissue scattering estimations used in the reconstructionmore » of the CW data. Scattering estimates were perturbed to study the effects on hemoglobin recovery. Breast mimicking agar phantoms with inclusions were imaged using the combined DBT/NIRST system for comparison with simulation results. Results: Patient simulations derived from DBT images show successful reconstruction of both normal and malignant lesions in the breast. They also demonstrate the importance of accurately quantifying tissue scattering. Specifically, 20% errors in optical scattering resulted in 22.6% or 35.1% error in quantification of total hemoglobin concentrations, depending on whether scattering was over- or underestimated, respectively. Limited frequency-domain optical signal sampling provided two regions scattering estimates (for fat and fibroglandular tissues) that led to hemoglobin concentrations that reduced the error in the tumor region by 31% relative to when a single estimate of optical scattering was used throughout the breast volume of interest. Acquiring frequency-domain data with six wavelengths instead of three did not significantly improve the hemoglobin concentration estimates. Simulation results were confirmed through experiments in two-region breast mimicking gelatin phantoms. Conclusions: Accurate characterization of scattering is necessary for quantification of hemoglobin. Based on this study, a system design is described to optimally combine breast tomosynthesis with NIRST.« less

The Relationship of Three-Dimensional Human Skull Motion to Brain Tissue Deformation in Magnetic Resonance Elastography Studies

PubMed Central

Badachhape, Andrew A.; Okamoto, Ruth J.; Durham, Ramona S.; Efron, Brent D.; Nadell, Sam J.; Johnson, Curtis L.; Bayly, Philip V.

2017-01-01

In traumatic brain injury (TBI), membranes such as the dura mater, arachnoid mater, and pia mater play a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is an imaging technique developed for noninvasive estimation of soft tissue material parameters. In MRE, dynamic deformation of brain tissue is induced by skull vibrations during magnetic resonance imaging (MRI); however, skull motion and its mode of transmission to the brain remain largely uncharacterized. In this study, displacements of points in the skull, reconstructed using data from an array of MRI-safe accelerometers, were compared to displacements of neighboring material points in brain tissue, estimated from MRE measurements. Comparison of the relative amplitudes, directions, and temporal phases of harmonic motion in the skulls and brains of six human subjects shows that the skull–brain interface significantly attenuates and delays transmission of motion from skull to brain. In contrast, in a cylindrical gelatin “phantom,” displacements of the rigid case (reconstructed from accelerometer data) were transmitted to the gelatin inside (estimated from MRE data) with little attenuation or phase lag. This quantitative characterization of the skull–brain interface will be valuable in the parameterization and validation of computer models of TBI. PMID:28267188

The Relationship of Three-Dimensional Human Skull Motion to Brain Tissue Deformation in Magnetic Resonance Elastography Studies.

PubMed

Badachhape, Andrew A; Okamoto, Ruth J; Durham, Ramona S; Efron, Brent D; Nadell, Sam J; Johnson, Curtis L; Bayly, Philip V

2017-05-01

In traumatic brain injury (TBI), membranes such as the dura mater, arachnoid mater, and pia mater play a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is an imaging technique developed for noninvasive estimation of soft tissue material parameters. In MRE, dynamic deformation of brain tissue is induced by skull vibrations during magnetic resonance imaging (MRI); however, skull motion and its mode of transmission to the brain remain largely uncharacterized. In this study, displacements of points in the skull, reconstructed using data from an array of MRI-safe accelerometers, were compared to displacements of neighboring material points in brain tissue, estimated from MRE measurements. Comparison of the relative amplitudes, directions, and temporal phases of harmonic motion in the skulls and brains of six human subjects shows that the skull-brain interface significantly attenuates and delays transmission of motion from skull to brain. In contrast, in a cylindrical gelatin "phantom," displacements of the rigid case (reconstructed from accelerometer data) were transmitted to the gelatin inside (estimated from MRE data) with little attenuation or phase lag. This quantitative characterization of the skull-brain interface will be valuable in the parameterization and validation of computer models of TBI.

Two-dimensional and 3-D images of thick tissue using time-constrained times-of-flight and absorbance spectrophotometry

NASA Astrophysics Data System (ADS)

Benaron, David A.; Lennox, M.; Stevenson, David K.

1992-05-01

Reconstructing deep-tissue images in real time using spectrophotometric data from optically diffusing thick tissues has been problematic. Continuous wave applications (e.g., pulse oximetry, regional cerebral saturation) ignore both the multiple paths traveled by the photons through the tissue and the effects of scattering, allowing scalar measurements but only under limited conditions; interferometry works poorly in thick, highly-scattering media; frequency- modulated approaches may not allow full deconvolution of scattering and absorbance; and pulsed-light techniques allow for preservation of information regarding the multiple paths taken by light through the tissue, but reconstruction is both computation intensive and limited by the relative surface area available for detection of photons. We have developed a picosecond times-of-flight and absorbance (TOFA) optical system, time-constrained to measure only photons with a narrow range of path lengths and arriving within a narrow angel of the emitter-detector axis. The delay until arrival of the earliest arriving photons is a function of both the scattering and absorbance of the tissues in a direct line between the emitter and detector, reducing the influence of surrounding tissues. Measurement using a variety of emitter and detector locations produces spatial information which can be analyzed in a standard 2-D grid, or subject to computer reconstruction to produce tomographic images representing 3-D structure. Using such a technique, we have been able to demonstrate the principles of tc-TOFA, detect and localize diffusive and/or absorptive objects suspended in highly scattering media (such as blood admixed with yeast), and perform simple 3-D reconstructions using phantom objects. We are now attempting to obtain images in vivo. Potential future applications include use as a research tool, and as a continuous, noninvasive, nondestructive monitor in diagnostic imaging, fetal monitoring, neurologic and cardiac assessment. The technique may lead to real-time optical imaging and quantitation of tissues oxygen delivery.

Light source distribution and scattering phase function influence light transport in diffuse multi-layered media

NASA Astrophysics Data System (ADS)

Vaudelle, Fabrice; L'Huillier, Jean-Pierre; Askoura, Mohamed Lamine

2017-06-01

Red and near-Infrared light is often used as a useful diagnostic and imaging probe for highly scattering media such as biological tissues, fruits and vegetables. Part of diffusively reflected light gives interesting information related to the tissue subsurface, whereas light recorded at further distances may probe deeper into the interrogated turbid tissues. However, modelling diffusive events occurring at short source-detector distances requires to consider both the distribution of the light sources and the scattering phase functions. In this report, a modified Monte Carlo model is used to compute light transport in curved and multi-layered tissue samples which are covered with a thin and highly diffusing tissue layer. Different light source distributions (ballistic, diffuse or Lambertian) are tested with specific scattering phase functions (modified or not modified Henyey-Greenstein, Gegenbauer and Mie) to compute the amount of backscattered and transmitted light in apple and human skin structures. Comparisons between simulation results and experiments carried out with a multispectral imaging setup confirm the soundness of the theoretical strategy and may explain the role of the skin on light transport in whole and half-cut apples. Other computational results show that a Lambertian source distribution combined with a Henyey-Greenstein phase function provides a higher photon density in the stratum corneum than in the upper dermis layer. Furthermore, it is also shown that the scattering phase function may affect the shape and the magnitude of the Bidirectional Reflectance Distribution (BRDF) exhibited at the skin surface.

Automated detection of esophageal dysplasia in in vivo optical coherence tomography images of the human esophagus

NASA Astrophysics Data System (ADS)

Kassinopoulos, Michalis; Dong, Jing; Tearney, Guillermo J.; Pitris, Costas

2018-02-01

Catheter-based Optical Coherence Tomography (OCT) devices allow real-time and comprehensive imaging of the human esophagus. Hence, they provide the potential to overcome some of the limitations of endoscopy and biopsy, allowing earlier diagnosis and better prognosis for esophageal adenocarcinoma patients. However, the large number of images produced during every scan makes manual evaluation of the data exceedingly difficult. In this study, we propose a fully automated tissue characterization algorithm, capable of discriminating normal tissue from Barrett's Esophagus (BE) and dysplasia through entire three-dimensional (3D) data sets, acquired in vivo. The method is based on both the estimation of the scatterer size of the esophageal epithelial cells, using the bandwidth of the correlation of the derivative (COD) method, as well as intensity-based characteristics. The COD method can effectively estimate the scatterer size of the esophageal epithelium cells in good agreement with the literature. As expected, both the mean scatterer size and its standard deviation increase with increasing severity of disease (i.e. from normal to BE to dysplasia). The differences in the distribution of scatterer size for each tissue type are statistically significant, with a p value of < 0.0001. However, the scatterer size by itself cannot be used to accurately classify the various tissues. With the addition of intensity-based statistics the correct classification rates for all three tissue types range from 83 to 100% depending on the lesion size.

High-sensitivity terahertz imaging of traumatic brain injury in a rat model

NASA Astrophysics Data System (ADS)

Zhao, Hengli; Wang, Yuye; Chen, Linyu; Shi, Jia; Ma, Kang; Tang, Longhuang; Xu, Degang; Yao, Jianquan; Feng, Hua; Chen, Tunan

2018-03-01

We demonstrated that different degrees of experimental traumatic brain injury (TBI) can be differentiated clearly in fresh slices of rat brain tissues using transmission-type terahertz (THz) imaging system. The high absorption region in THz images corresponded well with the injured area in visible images and magnetic resonance imaging results. The THz image and absorption characteristics of dehydrated paraffin-embedded brain slices and the hematoxylin and eosin (H&E)-stained microscopic images were investigated to account for the intrinsic differences in the THz images for the brain tissues suffered from different degrees of TBI and normal tissue aside from water. The THz absorption coefficients of rat brain tissues showed an increase in the aggravation of brain damage, particularly in the high-frequency range, whereas the cell density decreased as the order of mild, moderate, and severe TBI tissues compared with the normal tissue. Our results indicated that the different degrees of TBI were distinguishable owing to the different water contents and probable hematoma components distribution rather than intrinsic cell intensity. These promising results suggest that THz imaging has great potential as an alternative method for the fast diagnosis of TBI.

Effects of high-pressure oxygen therapy on brain tissue water content and AQP4 expression in rabbits with cerebral hemorrhage.

PubMed

Wu, Jing; Chen, Jiong; Guo, Hua; Peng, Fang

2014-12-01

To investigate the effects of different atmosphere absolutes (ATA) of high-pressure oxygen (HPO) on brain tissue water content and Aquaporin-4 (AQP4) expression in rabbits with cerebral hemorrhage. 180 New Zealand white rabbits were selected and randomly divided into normal group (n = 30), control group (n = 30) and cerebral hemorrhage group (n = 120), and cerebral hemorrhage group was divided into group A, B, C and D with 30 rabbits in each group. The groups received 1.0, 1.8, 2.0 and 2.2 ATA of HPO treatments, respectively. Ten rabbits in each group were killed at first, third and fifth day to detect the brain tissue water content and change of AQP4 expression. In cerebral hemorrhage group, brain tissue water content and AQP4 expression after model establishment were first increased, then decreased and reached the maximum on third day (p < 0.05). Brain tissue water content and AQP4 expression in control group and cerebral hemorrhage group were significantly higher than normal group at different time points (p < 0.05). In contrast, brain tissue water content and AQP4 expression in group C were significantly lower than in group A, group B, group D and control group (p < 0.05). In control group, AQP4-positive cells significantly increased after model establishment, which reached maximum on third day, and positive cells in group C were significantly less than in group A, group B and group D. We also found that AQP4 expression were positively correlated with brain tissue water content (r = 0.719, p < 0.05) demonstrated by significantly increased AQP4 expression along with increased brain tissue water content. In conclusion, HPO can decrease AQP4 expression in brain tissue of rabbits with cerebral hemorrhage to suppress the progression of brain edema and promote repairing of injured tissue. 2.0 ATA HPO exerts best effects, which provides an experimental basis for ATA selection of HPO in treating cerebral hemorrhage.

Cone-beam CT of traumatic brain injury using statistical reconstruction with a post-artifact-correction noise model

NASA Astrophysics Data System (ADS)

Dang, H.; Stayman, J. W.; Sisniega, A.; Xu, J.; Zbijewski, W.; Yorkston, J.; Aygun, N.; Koliatsos, V.; Siewerdsen, J. H.

2015-03-01

Traumatic brain injury (TBI) is a major cause of death and disability. The current front-line imaging modality for TBI detection is CT, which reliably detects intracranial hemorrhage (fresh blood contrast 30-50 HU, size down to 1 mm) in non-contrast-enhanced exams. Compared to CT, flat-panel detector (FPD) cone-beam CT (CBCT) systems offer lower cost, greater portability, and smaller footprint suitable for point-of-care deployment. We are developing FPD-CBCT to facilitate TBI detection at the point-of-care such as in emergent, ambulance, sports, and military applications. However, current FPD-CBCT systems generally face challenges in low-contrast, soft-tissue imaging. Model-based reconstruction can improve image quality in soft-tissue imaging compared to conventional filtered back-projection (FBP) by leveraging high-fidelity forward model and sophisticated regularization. In FPD-CBCT TBI imaging, measurement noise characteristics undergo substantial change following artifact correction, resulting in non-negligible noise amplification. In this work, we extend the penalized weighted least-squares (PWLS) image reconstruction to include the two dominant artifact corrections (scatter and beam hardening) in FPD-CBCT TBI imaging by correctly modeling the variance change following each correction. Experiments were performed on a CBCT test-bench using an anthropomorphic phantom emulating intra-parenchymal hemorrhage in acute TBI, and the proposed method demonstrated an improvement in blood-brain contrast-to-noise ratio (CNR = 14.2) compared to FBP (CNR = 9.6) and PWLS using conventional weights (CNR = 11.6) at fixed spatial resolution (1 mm edge-spread width at the target contrast). The results support the hypothesis that FPD-CBCT can fulfill the image quality requirements for reliable TBI detection, using high-fidelity artifact correction and statistical reconstruction with accurate post-artifact-correction noise models.

Introducing nuclei scatterer patterns into histology based intravascular ultrasound simulation framework

NASA Astrophysics Data System (ADS)

Kraft, Silvan; Karamalis, Athanasios; Sheet, Debdoot; Drecoll, Enken; Rummeny, Ernst J.; Navab, Nassir; Noël, Peter B.; Katouzian, Amin

2013-03-01

Medical ultrasonic grayscale images are formed from acoustic waves following their interactions with distributed scatterers within tissues media. For accurate simulation of acoustic wave propagation, a reliable model describing unknown parameters associated with tissues scatterers such as distribution, size and acoustic properties is essential. In this work, we introduce a novel approach defining ultrasonic scatterers by incorporating a distribution of cellular nuclei patterns in biological tissues to simulate ultrasonic response of atherosclerotic tissues in intravascular ultrasound (IVUS). For this reason, a virtual phantom is generated through manual labeling of different tissue types (fibrotic, lipidic and calcified) on histology sections. Acoustic properties of each tissue type are defined by assuming that the ultrasound signal is primarily backscattered by the nuclei of the organic cells within the intima and media of the vessel wall. This resulting virtual phantom is subsequently used to simulate ultrasonic wave propagation through the tissue medium computed using finite difference estimation. Subsequently B-mode images for a specific histological section are processed from the simulated radiofrequency (RF) data and compared with the original IVUS of the same tissue section. Real IVUS RF signals for these histological sections were obtained using a single-element mechanically rotating 40MHz transducer. Evaluation is performed by trained reviewers subjectively assessing both simulated and real B-mode IVUS images. Our simulation platform provides a high image quality with a very promising correlation to the original IVUS images. This will facilitate to better understand progression of such a chronic disease from micro-level and its integration into cardiovascular disease-specific models.

A novel non-imaging optics based Raman spectroscopy device for transdermal blood analyte measurement

PubMed Central

Kong, Chae-Ryon; Barman, Ishan; Dingari, Narahara Chari; Kang, Jeon Woong; Galindo, Luis; Dasari, Ramachandra R.; Feld, Michael S.

2011-01-01

Due to its high chemical specificity, Raman spectroscopy has been considered to be a promising technique for non-invasive disease diagnosis. However, during Raman excitation, less than one out of a million photons undergo spontaneous Raman scattering and such weakness in Raman scattered light often require highly efficient collection of Raman scattered light for the analysis of biological tissues. We present a novel non-imaging optics based portable Raman spectroscopy instrument designed for enhanced light collection. While the instrument was demonstrated on transdermal blood glucose measurement, it can also be used for detection of other clinically relevant blood analytes such as creatinine, urea and cholesterol, as well as other tissue diagnosis applications. For enhanced light collection, a non-imaging optical element called compound hyperbolic concentrator (CHC) converts the wide angular range of scattered photons (numerical aperture (NA) of 1.0) from the tissue into a limited range of angles accommodated by the acceptance angles of the collection system (e.g., an optical fiber with NA of 0.22). A CHC enables collimation of scattered light directions to within extremely narrow range of angles while also maintaining practical physical dimensions. Such a design allows for the development of a very efficient and compact spectroscopy system for analyzing highly scattering biological tissues. Using the CHC-based portable Raman instrument in a clinical research setting, we demonstrate successful transdermal blood glucose predictions in human subjects undergoing oral glucose tolerance tests. PMID:22125761

Monte Carlo Simulations of Arterial Imaging with Optical Coherence Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amendt, P.; Estabrook, K.; Everett, M.

2000-02-01

The laser-tissue interaction code LATIS [London et al., Appl. Optics 36, 9068 ( 1998)] is used to analyze photon scattering histories representative of optical coherence tomography (OCT) experiment performed at Lawrence Livermore National Laboratory. Monte Carlo photonics with Henyey-Greenstein anisotropic scattering is implemented and used to simulate signal discrimination of intravascular structure. An analytic model is developed and used to obtain a scaling law relation for optimization of the OCT signal and to validate Monte Carlo photonics. The appropriateness of the Henyey-Greenstein phase function is studied by direct comparison with more detailed Mie scattering theory using an ensemble of sphericalmore » dielectric scatterers. Modest differences are found between the two prescriptions for describing photon angular scattering in tissue. In particular, the Mie scattering phase functions provide less overall reflectance signal but more signal contrast compared to the Henyey-Greenstein formulation.« less

Monitoring brain temperature by time-resolved near-infrared spectroscopy: pilot study

NASA Astrophysics Data System (ADS)

Bakhsheshi, Mohammad Fazel; Diop, Mamadou; St. Lawrence, Keith; Lee, Ting-Yim

2014-05-01

Mild hypothermia (HT) is an effective neuroprotective strategy for a variety of acute brain injuries. However, the wide clinical adaptation of HT has been hampered by the lack of a reliable noninvasive method for measuring brain temperature, since core measurements have been shown to not always reflect brain temperature. The goal of this work was to develop a noninvasive optical technique for measuring brain temperature that exploits both the temperature dependency of water absorption and the high concentration of water in brain (80%-90%). Specifically, we demonstrate the potential of time-resolved near-infrared spectroscopy (TR-NIRS) to measure temperature in tissue-mimicking phantoms (in vitro) and deep brain tissue (in vivo) during heating and cooling, respectively. For deep brain tissue temperature monitoring, experiments were conducted on newborn piglets wherein hypothermia was induced by gradual whole body cooling. Brain temperature was concomitantly measured by TR-NIRS and a thermocouple probe implanted in the brain. Our proposed TR-NIRS method was able to measure the temperature of tissue-mimicking phantoms and brain tissues with a correlation of 0.82 and 0.66 to temperature measured with a thermometer, respectively. The mean difference between the TR-NIRS and thermometer measurements was 0.15°C±1.1°C for the in vitro experiments and 0.5°C±1.6°C for the in vivo measurements.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain.

PubMed

Taoka, Toshiaki; Naganawa, Shinji

2018-04-10

After Kanda's first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the 'glymphatic system', which is a coined word that combines 'gl' for glia cell and 'lymphatic' system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain

PubMed Central

Taoka, Toshiaki; Naganawa, Shinji

2018-01-01

After Kanda’s first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the ‘glymphatic system’, which is a coined word that combines ‘gl’ for glia cell and ‘lymphatic’ system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue. PMID:29367513

Tissue characterization with ballistic photons: counting scattering and/or absorption centres

NASA Astrophysics Data System (ADS)

Corral, F.; Strojnik, M.; Paez, G.

2015-03-01

We describe a new method to separate ballistic from the scattered photons for optical tissue characterization. It is based on the hypothesis that the scattered photons acquire a phase delay. The photons passing through the sample without scattering or absorption preserve their coherence so they may participate in interference. We implement a Mach-Zehnder experimental setup where the ballistic photons pass through the sample with the delay caused uniquely by the sample indices of refraction. We incorporate a movable mirror on the piezoelectric actuator in the sample arm to detect the amplitude of the modulation term. We present the theory that predicts the path-integrated (or total) concentration of the scattering and absorption centres. The proposed technique may characterize samples with transmission attenuation of ballistic photons by a factor of 10-14.

Proton radiography for inline treatment planning and positioning verification of small animals.

PubMed

Müller, Johannes; Neubert, Christian; von Neubeck, Cläre; Baumann, Michael; Krause, Mechthild; Enghardt, Wolfgang; Bütof, Rebecca; Dietrich, Antje; Lühr, Armin

2017-11-01

As proton therapy becomes increasingly well established, there is a need for high-quality clinically relevant in vivo data to gain better insight into the radiobiological effects of proton irradiation on both healthy and tumor tissue. This requires the development of easily applicable setups that allow for efficient, fractionated, image-guided proton irradiation of small animals, the most widely used pre-clinical model. Here, a method is proposed to perform dual-energy proton radiography for inline positioning verification and treatment planning. Dual-energy proton radiography exploits the differential enhancement of object features in two successively measured two-dimensional (2D) dose distributions at two different proton energies. The two raw images show structures that are dominated by energy absorption (absorption mode) or scattering (scattering mode) of protons in the object, respectively. Data post-processing allowed for the separation of both signal contributions in the respective images. The images were evaluated regarding recognizable object details and feasibility of rigid registration to acquired planar X-ray scans. Robust, automated rigid registration of proton radiography and planar X-ray images in scattering mode could be reliably achieved with the animal bedding unit used as registration landmark. Distinguishable external and internal features of the imaged mouse included the outer body contour, the skull with substructures, the lung, abdominal structures and the hind legs. Image analysis based on the combined information of both imaging modes allowed image enhancement and calculation of 2D water-equivalent path length (WEPL) maps of the object along the beam direction. Fractionated irradiation of exposed target volumes (e.g., subcutaneous tumor model or brain) can be realized with the suggested method being used for daily positioning and range determination. Robust registration of X-ray and proton radiography images allows for the irradiation of tumor entities that require conventional computed tomography (CT)-based planning, such as orthotopic lung or brain tumors, similar to conventional patient treatment.

Mathematical modelling of blood-brain barrier failure and edema

NASA Astrophysics Data System (ADS)

Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

2015-11-01

Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

Responses of the Human Brain to Mild Dehydration and Rehydration Explored In Vivo by 1H-MR Imaging and Spectroscopy.

PubMed

Biller, A; Reuter, M; Patenaude, B; Homola, G A; Breuer, F; Bendszus, M; Bartsch, A J

2015-12-01

As yet, there are no in vivo data on tissue water changes and associated morphometric changes involved in the osmo-adaptation of normal brains. Our aim was to evaluate osmoadaptive responses of the healthy human brain to osmotic challenges of de- and rehydration by serial measurements of brain volume, tissue fluid, and metabolites. Serial T1-weighted and (1)H-MR spectroscopy data were acquired in 15 healthy individuals at normohydration, on 12 hours of dehydration, and during 1 hour of oral rehydration. Osmotic challenges were monitored by serum measures, including osmolality and hematocrit. MR imaging data were analyzed by using FreeSurfer and LCModel. On dehydration, serum osmolality increased by 0.67% and brain tissue fluid decreased by 1.63%, on average. MR imaging morphometry demonstrated corresponding decreases of cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus. These changes reversed during rehydration. Continuous fluid ingestion of 1 L of water for 1 hour within the scanner lowered serum osmolality by 0.96% and increased brain tissue fluid by 0.43%, on average. Concomitantly, cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus increased. Changes in brain tissue fluid were related to volume changes of the whole brain, the white matter, and hypothalamus/thalamus. Only volume changes of the hypothalamus/thalamus significantly correlated with serum osmolality. This is the first study simultaneously evaluating changes in brain tissue fluid, metabolites, volume, and cortical thickness. Our results reflect cellular volume regulatory mechanisms at a macroscopic level and emphasize that it is essential to control for hydration levels in studies on brain morphometry and metabolism in order to avoid confounding the findings. © 2015 by American Journal of Neuroradiology.

Probing neural tissue with airy light-sheet microscopy: investigation of imaging performance at depth within turbid media

NASA Astrophysics Data System (ADS)

Nylk, Jonathan; McCluskey, Kaley; Aggarwal, Sanya; Tello, Javier A.; Dholakia, Kishan

2017-02-01

Light-sheet microscopy (LSM) has received great interest for fluorescent imaging applications in biomedicine as it facilitates three-dimensional visualisation of large sample volumes with high spatiotemporal resolution whilst minimising irradiation of, and photo-damage to the specimen. Despite these advantages, LSM can only visualize superficial layers of turbid tissues, such as mammalian neural tissue. Propagation-invariant light modes have played a key role in the development of high-resolution LSM techniques as they overcome the natural divergence of a Gaussian beam, enabling uniform and thin light-sheets over large distances. Most notably, Bessel and Airy beam-based light-sheet imaging modalities have been demonstrated. In the single-photon excitation regime and in lightly scattering specimens, Airy-LSM has given competitive performance with advanced Bessel-LSM techniques. Airy and Bessel beams share the property of self-healing, the ability of the beam to regenerate its transverse beam profile after propagation around an obstacle. Bessel-LSM techniques have been shown to increase the penetration-depth of the illumination into turbid specimens but this effect has been understudied in biologically relevant tissues, particularly for Airy beams. It is expected that Airy-LSM will give a similar enhancement over Gaussian-LSM. In this paper, we report on the comparison of Airy-LSM and Gaussian-LSM imaging modalities within cleared and non-cleared mouse brain tissue. In particular, we examine image quality versus tissue depth by quantitative spatial Fourier analysis of neural structures in virally transduced fluorescent tissue sections, showing a three-fold enhancement at 50 μm depth into non-cleared tissue with Airy-LSM. Complimentary analysis is performed by resolution measurements in bead-injected tissue sections.

Portable Wideband Microwave Imaging System for Intracranial Hemorrhage Detection Using Improved Back-projection Algorithm with Model of Effective Head Permittivity

PubMed Central

Mobashsher, Ahmed Toaha; Mahmoud, A.; Abbosh, A. M.

2016-01-01

Intracranial hemorrhage is a medical emergency that requires rapid detection and medication to restrict any brain damage to minimal. Here, an effective wideband microwave head imaging system for on-the-spot detection of intracranial hemorrhage is presented. The operation of the system relies on the dielectric contrast between healthy brain tissues and a hemorrhage that causes a strong microwave scattering. The system uses a compact sensing antenna, which has an ultra-wideband operation with directional radiation, and a portable, compact microwave transceiver for signal transmission and data acquisition. The collected data is processed to create a clear image of the brain using an improved back projection algorithm, which is based on a novel effective head permittivity model. The system is verified in realistic simulation and experimental environments using anatomically and electrically realistic human head phantoms. Quantitative and qualitative comparisons between the images from the proposed and existing algorithms demonstrate significant improvements in detection and localization accuracy. The radiation and thermal safety of the system are examined and verified. Initial human tests are conducted on healthy subjects with different head sizes. The reconstructed images are statistically analyzed and absence of false positive results indicate the efficacy of the proposed system in future preclinical trials. PMID:26842761

Portable Wideband Microwave Imaging System for Intracranial Hemorrhage Detection Using Improved Back-projection Algorithm with Model of Effective Head Permittivity

NASA Astrophysics Data System (ADS)

Mobashsher, Ahmed Toaha; Mahmoud, A.; Abbosh, A. M.

2016-02-01

Intracranial hemorrhage is a medical emergency that requires rapid detection and medication to restrict any brain damage to minimal. Here, an effective wideband microwave head imaging system for on-the-spot detection of intracranial hemorrhage is presented. The operation of the system relies on the dielectric contrast between healthy brain tissues and a hemorrhage that causes a strong microwave scattering. The system uses a compact sensing antenna, which has an ultra-wideband operation with directional radiation, and a portable, compact microwave transceiver for signal transmission and data acquisition. The collected data is processed to create a clear image of the brain using an improved back projection algorithm, which is based on a novel effective head permittivity model. The system is verified in realistic simulation and experimental environments using anatomically and electrically realistic human head phantoms. Quantitative and qualitative comparisons between the images from the proposed and existing algorithms demonstrate significant improvements in detection and localization accuracy. The radiation and thermal safety of the system are examined and verified. Initial human tests are conducted on healthy subjects with different head sizes. The reconstructed images are statistically analyzed and absence of false positive results indicate the efficacy of the proposed system in future preclinical trials.

Ginsenoside Rg1 nanoparticle penetrating the blood-brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction.

PubMed

Shen, Junyi; Zhao, Zhiming; Shang, Wei; Liu, Chunli; Zhang, Beibei; Zhao, Lingjie; Cai, Hui

2017-01-01

Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood-brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction.

Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

PubMed Central

Shen, Junyi; Zhao, Zhiming; Shang, Wei; Liu, Chunli; Zhang, Beibei; Zhao, Lingjie; Cai, Hui

2017-01-01

Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood–brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction. PMID:28919749

Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir

2014-08-15

The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractionsmore » from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.« less

Quantitative 1D diffraction signatures during dual detector scatter VOI breast CBCT

NASA Astrophysics Data System (ADS)

LeClair, Robert J.

2017-03-01

Dual detector VOI scatter CBCT is similar to dual detector VOI CBCT except that during the high resolution scan, the low resolution flat panel detector is also used to capture the scattered photons. Simulations show a potential use of scatter to diagnose suspicious VOIs. Energy integrated signals due to scatter (EISs) were computed for a specific imaging task involving a malignant lesion and was labelled as a hypothetical experiment (expt) result. The signal was compared to predictions (pred) using benign and malignant lesions. The ΔEISs=EISs|expt - EISs|pred displayed eye catching diffraction structure when the prediction calculation used a benign lesion. The structure occurred even when the phantom compositions were different for prediction and experiment calculations. Since the diffraction structure has a circularly symmetric behaviour because the tissues are amorphous in nature, the 2D ΔEISs patterns were transformed to 1D signals. The 1D signals were obtained by calculating the mean ΔEISs signals in rings. The mean pixel values were a function of the momentum transfer argument q = 4π sin(θ/2)/λ which ranged from 12 to 46 nm-1. The 1D signals correlated well with the 2D profiles. Of particular interest were scatter signatures between q = 20 and 30 nm-1 where malignant tissue is predicted to scatter more than benign fibroglandular tissue. The 1D diffraction signatures could allow a better method to diagnose a suspicious lesion during dual detector scatter VOI CBCT.

Noninvasive identification of bladder cancer with sub-surface backscattered light

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bigio, I.J.; Mourant, J.R.; Boyer, J.

1994-02-01

A non-invasive diagnostic tool that could identify malignancy in situ and in real time would have a major impact on the detection and treatment of cancer. We have developed and are testing early prototypes of an optical biopsy system (OBS) for detection of cancer and other tissue pathologies. The OBS invokes a unique approach to optical diagnosis of tissue pathologies based on the elastic scattering properties, over a wide range of wavelengths, of the microscopic structure of the tissue. Absorption bands in the tissue also add useful complexity to the spectral data collected. The use of elastic scattering as themore » key to optical tissue diagnostics in the OBS is based on the fact that many tissue pathologies, including a majority of cancer forms, manifest significant architectural changes at the cellular and sub-cellular level. Since the cellular components that cause elastic scattering have dimensions typically on the order of visible to near-IR wavelengths, the elastic (Mie) scattering properties will be strongly wavelength dependent. Thus, morphology and size changes can be expected to cause significant changes in an optical signature that is derived from the wavelength-dependence of elastic scattering as well as absorption. The data acquisition and storage/display time with the OBS instrument is {approximately}1 second. Thus, in addition to the reduced invasiveness of this technique compared with current state-of-the-art methods (surgical biopsy and pathology analysis), the OBS offers the possibility of impressively faster diagnostic assessment. The OBS employs a small fiber-optic probe that is amenable to use with any endoscope, catheter or hypodermic, or to direct surface examination (e.g., as in skin cancer or cervical cancer). We report here specifically on its potential application in the detection of bladder cancer.« less

Optical characterization of tissue mimicking phantoms by a vertical double integrating sphere system

NASA Astrophysics Data System (ADS)

Han, Yilin; Jia, Qiumin; Shen, Shuwei; Liu, Guangli; Guo, Yuwei; Zhou, Ximing; Chu, Jiaru; Zhao, Gang; Dong, Erbao; Allen, David W.; Lemaillet, Paul; Xu, Ronald

2016-03-01

Accurate characterization of absorption and scattering properties for biologic tissue and tissue-simulating materials enables 3D printing of traceable tissue-simulating phantoms for medical spectral device calibration and standardized medical optical imaging. Conventional double integrating sphere systems have several limitations and are suboptimal for optical characterization of liquid and soft materials used in 3D printing. We propose a vertical double integrating sphere system and the associated reconstruction algorithms for optical characterization of phantom materials that simulate different human tissue components. The system characterizes absorption and scattering properties of liquid and solid phantom materials in an operating wavelength range from 400 nm to 1100 nm. Absorption and scattering properties of the phantoms are adjusted by adding titanium dioxide powder and India ink, respectively. Different material compositions are added in the phantoms and characterized by the vertical double integrating sphere system in order to simulate the human tissue properties. Our test results suggest that the vertical integrating sphere system is able to characterize optical properties of tissue-simulating phantoms without precipitation effect of the liquid samples or wrinkling effect of the soft phantoms during the optical measurement.

Tissue specific specialization of the nanoscale architecture of Arabidopsis.

PubMed

Liu, Jiliang; Inouye, Hideyo; Venugopalan, Nagarajan; Fischetti, Robert F; Gleber, S Charlotte; Vogt, Stefan; Cusumano, Joanne C; Kim, Jeong Im; Chapple, Clint; Makowski, Lee

2013-11-01

The Arabidopsis stem is composed of five tissues - the pith, xylem, phloem, cortex and epidermis - each of which fulfills specific roles in support of the growth and survival of the organism. The lignocellulosic scaffolding of cell walls is specialized to provide optimal support for the diverse functional roles of these layers, but little is known about this specialization. X-ray scattering can be used to study this tissue-specific diversity because the cellulosic components of the cell walls give rise to recognizable scattering features interpretable in terms of the underlying molecular architecture and distinct from the largely unoriented scatter from other constituents. Here we use scanning X-ray microdiffraction from thin sections to characterize the diversity of molecular architecture in the Arabidopsis stem and correlate that diversity to the functional roles the distinct tissues of the stem play in the growth and survival of the organism. Copyright © 2013. Published by Elsevier Inc.

Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child

PubMed Central

Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

2015-01-01

Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters. PMID:26495031

Brain cancer probed by native fluorescence and stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; He, Yong; Pu, Yang; Li, Qingbo; Wang, Wei; Alfano, Robert R.

2012-12-01

Optical biopsy spectroscopy was applied to diagnosis human brain cancer in vitro. The spectra of native fluorescence, Stokes shift and excitation spectra were obtained from malignant meningioma, benign, normal meningeal tissues and acoustic neuroma benign tissues. The wide excitation wavelength ranges were used to establish the criterion for distinguishing brain diseases. The alteration of fluorescence spectra between normal and abnormal brain tissues were identified by the characteristic fluorophores under the excitation with UV to visible wavelength range. It was found that the ratios of the peak intensities and peak position in both spectra of fluorescence and Stokes shift may be used to diagnose human brain meninges diseases. The preliminary analysis of fluorescence spectral data from cancer and normal meningeal tissues by basic biochemical component analysis model (BBCA) and Bayes classification model based on statistical methods revealed the changes of components, and classified the difference between cancer and normal human brain meningeal tissues in a predictions accuracy rate is 0.93 in comparison with histopathology and immunohistochemistry reports (gold standard).

Characterizing tissue microstructure using an ultrasound system-independent spatial autocorrelation function

NASA Astrophysics Data System (ADS)

Dong, Fang

1999-09-01

The research described in this dissertation is related to characterization of tissue microstructure using a system- independent spatial autocorrelation function (SAF). The function was determined using a reference phantom method, which employed a well-defined ``point- scatterer'' reference phantom to account for instrumental factors. The SAF's were estimated for several tissue-mimicking (TM) phantoms and fresh dog livers. Both phantom tests and in vitro dog liver measurements showed that the reference phantom method is relatively simple and fairly accurate, providing the bandwidth of the measurement system is sufficient for the size of the scatterer being involved in the scattering process. Implementation of this method in clinical scanner requires that distortions from patient's body wall be properly accounted for. The SAF's were estimated for two phantoms with body-wall-like distortions. The experimental results demonstrated that body wall distortions have little effect if echo data are acquired from a large scattering volume. One interesting application of the SAF is to form a ``scatterer size image''. The scatterer size image may help providing diagnostic tools for those diseases in which the tissue microstructure is different from the normal. Another method, the BSC method, utilizes information contained in the frequency dependence of the backscatter coefficient to estimate the scatterer size. The SAF technique produced accurate scatterer size images of homogeneous TM phantoms and the BSC method was capable of generating accurate size images for heterogeneous phantoms. In the scatterer size image of dog kidneys, the contrast-to-noise-ratio (CNR) between renal cortex and medulla was improved dramatically compared to the gray- scale image. The effect of nonlinear propagation was investigated by using a custom-designed phantom with overlaying TM fat layer. The results showed that the correlation length decreased when the transmitting power increased. The measurement results support the assumption that nonlinear propagation generates harmonic energies and causes underestimation of scatterer diameters. Nonlinear propagation can be further enhanced by those materials with high B/A value-a parameter which characterizes the degree of nonlinearity. Nine versions of TM fat and non-fat materials were measured for their B/A values using a new measurement technique, the ``simplified finite amplitude insertion substitution'' (SFAIS) method.

Determination of effective atomic number of biomedical samples using Gamma ray back-scattering

NASA Astrophysics Data System (ADS)

Singh, Inderjeet; Singh, Bhajan; Sandhu, B. S.; Sabharwal, Arvind D.

2018-05-01

The study of effective atomic number of biomedical sample has been carried out by using a non-destructive multiple back-scattering technique. Also radiation characterization method is used to compare the tissue equivalent material as human tissue. Response function of 3″ × 3″ NaI(Tl) scintillation detector is implemented on recorded pulse-height distribution to boost the counts under the photo-peak and help to reduce the uncertainty in the experimental result. Monte Carlo calculation for multiple back-scattered events supports the reported experimental work.

Photoacoustic phasoscopy super-contrast imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Fei; Feng, Xiaohua; Zheng, Yuanjin, E-mail: yjzheng@ntu.edu.sg

2014-05-26

Phasoscopy is a recently proposed concept correlating electromagnetic (EM) absorption and scattering properties based on energy conservation. Phase information can be extracted from EM absorption induced acoustic wave and scattered EM wave for biological tissue characterization. In this paper, an imaging modality, termed photoacoustic phasoscopy imaging (PAPS), is proposed and verified experimentally based on phasoscopy concept with laser illumination. Both endogenous photoacoustic wave and scattered photons are collected simultaneously to extract the phase information. The PAPS images are then reconstructed on vessel-mimicking phantom and ex vivo porcine tissues to show significantly improved contrast than conventional photoacoustic imaging.

Contrast enhanced spectroscopic optical coherence tomography

NASA Technical Reports Server (NTRS)

Xu, Chenyang (Inventor); Boppart, Stephen A. (Inventor)

2010-01-01

A method of forming an image of a sample includes performing SOCT on a sample. The sample may include a contrast agent, which may include an absorbing agent and/or a scattering agent. A method of forming an image of tissue may include selecting a contrast agent, delivering the contrast agent to the tissue, acquiring SOCT data from the tissue, and converting the SOCT data into an image. The contributions to the SOCT data of an absorbing agent and a scattering agent in a sample may be quantified separately.

TU-G-210-02: TRANS-FUSIMO - An Integrative Approach to Model-Based Treatment Planning of Liver FUS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Preusser, T.

Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such asmore » the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)« less

Silver nanoparticle based surface enhanced Raman scattering spectroscopy of diabetic and normal rat pancreatic tissue under near-infrared laser excitation

NASA Astrophysics Data System (ADS)

Huang, H.; Shi, H.; Feng, S.; Lin, J.; Chen, W.; Huang, Z.; Li, Y.; Yu, Y.; Lin, D.; Xu, Q.; Chen, R.

2013-04-01

This paper presents the use of high spatial resolution silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) from rat pancreatic tissue to obtain biochrmical information about the tissue. A high quality SERS signal from a mixture of pancreatic tissues and silver nanoparticles can be obtained within 10 s using a Renishaw micro-Raman system. Prominent SERS bands of pancreatic tissue were assigned to known molecular vibrations, such as the vibrations of DNA bases, RNA bases, proteins and lipids. Different tissue structures of diabetic and normal rat pancreatic tissues have characteristic features in SERS spectra. This exploratory study demonstrated great potential for using SERS imaging to distinguish diabetic and normal pancreatic tissues on frozen sections without using dye labeling of functionalized binding sites.

Backscatter and attenuation properties of mammalian brain tissues

NASA Astrophysics Data System (ADS)

Wijekularatne, Pushpani Vihara

Traumatic Brain Injury (TBI) is a common category of brain injuries, which contributes to a substantial number of deaths and permanent disability all over the world. Ultrasound technology plays a major role in tissue characterization due to its low cost and portability that could be used to bridge a wide gap in the TBI diagnostic process. This research addresses the ultrasonic properties of mammalian brain tissues focusing on backscatter and attenuation. Orientation dependence and spatial averaging of data were analyzed using the same method resulting from insertion of tissue sample between a transducer and a reference reflector. Apparent backscatter transfer function (ABTF) at 1 to 10 MHz, attenuation coefficient and backscatter coefficient (BSC) at 1 to 5 MHz frequency ranges were measured on ovine brain tissue samples. The resulting ABTF was a monotonically decreasing function of frequency and the attenuation coefficient and BSC generally were increasing functions of frequency, results consistent with other soft tissues such as liver, blood and heart.

A Dense Poly(ethylene glycol) Coating Improves Penetration of Large Polymeric Nanoparticles within Brain Tissue

PubMed Central

Nance, Elizabeth A.; Woodworth, Graeme F.; Sailor, Kurt A.; Shih, Ting-Yu; Xu, Qingguo; Swaminathan, Ganesh; Xiang, Dennis; Eberhart, Charles; Hanes, Justin

2013-01-01

Prevailing opinion suggests that only substances up to 64 nm in diameter can move at appreciable rates through the brain extracellular space (ECS). This size range is large enough to allow diffusion of signaling molecules, nutrients, and metabolic waste products, but too small to allow efficient penetration of most particulate drug delivery systems and viruses carrying therapeutic genes, thereby limiting effectiveness of many potential therapies. We analyzed the movements of nanoparticles of various diameters and surface coatings within fresh human and rat brain tissue ex vivo and mouse brain in vivo. Nanoparticles as large as 114-nm in diameter diffused within the human and rat brain, but only if they were densely coated with poly(ethylene glycol) (PEG). Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm, and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles, spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible. PMID:22932224

Heterogeneity of the calcium-induced permeability transition in isolated non-synaptic brain mitochondria.

PubMed

Kristián, Tibor; Weatherby, Tina M; Bates, Timothy E; Fiskum, Gary

2002-12-01

Calcium overload of neural cell mitochondria plays a key role in excitotoxic and ischemic brain injury. This study tested the hypothesis that brain mitochondria consist of subpopulations with differential sensitivity to calcium-induced inner membrane permeability transition, and that this sensitivity is greatly reduced by physiological levels of adenine nucleotides. Isolated non-synaptosomal rat brain mitochondria were incubated in a potassium-based medium in the absence or presence of ATP or ADP. Measurements were made of medium and intramitochondrial free calcium, light scattering, mitochondrial ultrastructure, and the elemental composition of electron-opaque deposits within mitochondria treated with calcium. In the absence of adenine nucleotides, calcium induced a partial decrease in light scattering, accompanied by three distinct ultrastructural morphologies, including large-amplitude swelling, matrix vacuolization and a normal appearance. In the presence of ATP or ADP the mitochondrial calcium uptake capacity was greatly enhanced and calcium induced an increase rather than a decrease in mitochondrial light scattering. Approximately 10% of the mitochondria appeared damaged and the rest contained electron-dense precipitates that contained calcium, as determined by electron-energy loss spectroscopy. These results indicate that brain mitochondria are heterogeneous in their response to calcium. In the absence of adenine nucleotides, approximately 20% of the mitochondrial population exhibit morphological alterations consistent with activation of the permeability transition, but less than 10% exhibit evidence of osmotic swelling and membrane disruption in the presence of ATP or ADP.

A method to estimate the fractional fat volume within a ROI of a breast biopsy for WAXS applications: Animal tissue evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Robert Y., E-mail: rx-tang@laurentian.ca; McDonald, Nancy, E-mail: mcdnancye@gmail.com; Laamanen, Curtis, E-mail: cx-laamanen@laurentian.ca

Purpose: To develop a method to estimate the mean fractional volume of fat (ν{sup ¯}{sub fat}) within a region of interest (ROI) of a tissue sample for wide-angle x-ray scatter (WAXS) applications. A scatter signal from the ROI was obtained and use of ν{sup ¯}{sub fat} in a WAXS fat subtraction model provided a way to estimate the differential linear scattering coefficient μ{sub s} of the remaining fatless tissue. Methods: The efficacy of the method was tested using animal tissue from a local butcher shop. Formalin fixed samples, 5 mm in diameter 4 mm thick, were prepared. The two mainmore » tissue types were fat and meat (fibrous). Pure as well as composite samples consisting of a mixture of the two tissue types were analyzed. For the latter samples, ν{sub fat} for the tissue columns of interest were extracted from corresponding pixels in CCD digital x-ray images using a calibration curve. The means ν{sup ¯}{sub fat} were then calculated for use in a WAXS fat subtraction model. For the WAXS measurements, the samples were interrogated with a 2.7 mm diameter 50 kV beam and the 6° scattered photons were detected with a CdTe detector subtending a solid angle of 7.75 × 10{sup −5} sr. Using the scatter spectrum, an estimate of the incident spectrum, and a scatter model, μ{sub s} was determined for the tissue in the ROI. For the composite samples, a WAXS fat subtraction model was used to estimate the μ{sub s} of the fibrous tissue in the ROI. This signal was compared to μ{sub s} of fibrous tissue obtained using a pure fibrous sample. Results: For chicken and beef composites, ν{sup ¯}{sub fat}=0.33±0.05 and 0.32 ± 0.05, respectively. The subtractions of these fat components from the WAXS composite signals provided estimates of μ{sub s} for chicken and beef fibrous tissue. The differences between the estimates and μ{sub s} of fibrous obtained with a pure sample were calculated as a function of the momentum transfer x. A t-test showed that the mean of the differences did not vary from zero in a statistically significant way thereby validating the methods. Conclusions: The methodology to estimate ν{sup ¯}{sub fat} in a ROI of a tissue sample via CCD x-ray imaging was quantitatively accurate. The WAXS fat subtraction model allowed μ{sub s} of fibrous tissue to be obtained from a ROI which had some fat. The fat estimation method coupled with the WAXS models can be used to compare μ{sub s} coefficients of fibroglandular and cancerous breast tissue.« less

Wide-field three-photon excitation in biological samples

PubMed Central

Rowlands, Christopher J; Park, Demian; Bruns, Oliver T; Piatkevich, Kiryl D; Fukumura, Dai; Jain, Rakesh K; Bawendi, Moungi G; Boyden, Edward S; So, Peter TC

2017-01-01

Three-photon wide-field depth-resolved excitation is used to overcome some of the limitations in conventional point-scanning two- and three-photon microscopy. Excitation of chromophores as diverse as channelrhodopsins and quantum dots is shown, and a penetration depth of more than 700 μm into fixed scattering brain tissue is achieved, approximately twice as deep as that achieved using two-photon wide-field excitation. Compatibility with live animal experiments is confirmed by imaging the cerebral vasculature of an anesthetized mouse; a complete focal stack was obtained without any evidence of photodamage. As an additional validation of the utility of wide-field three-photon excitation, functional excitation is demonstrated by performing three-photon optogenetic stimulation of cultured mouse hippocampal neurons expressing a channelrhodopsin; action potentials could reliably be excited without causing photodamage. PMID:29152380

Determination of friction coefficient in unconfined compression of brain tissue.

PubMed

Rashid, Badar; Destrade, Michel; Gilchrist, Michael D

2012-10-01

Unconfined compression tests are more convenient to perform on cylindrical samples of brain tissue than tensile tests in order to estimate mechanical properties of the brain tissue because they allow homogeneous deformations. The reliability of these tests depends significantly on the amount of friction generated at the specimen/platen interface. Thus, there is a crucial need to find an approximate value of the friction coefficient in order to predict a possible overestimation of stresses during unconfined compression tests. In this study, a combined experimental-computational approach was adopted to estimate the dynamic friction coefficient μ of porcine brain matter against metal platens in compressive tests. Cylindrical samples of porcine brain tissue were tested up to 30% strain at variable strain rates, both under bonded and lubricated conditions in the same controlled environment. It was established that μ was equal to 0.09±0.03, 0.18±0.04, 0.18±0.04 and 0.20±0.02 at strain rates of 1, 30, 60 and 90/s, respectively. Additional tests were also performed to analyze brain tissue under lubricated and bonded conditions, with and without initial contact of the top platen with the brain tissue, with different specimen aspect ratios and with different lubricants (Phosphate Buffer Saline (PBS), Polytetrafluoroethylene (PTFE) and Silicone). The test conditions (lubricant used, biological tissue, loading velocity) adopted in this study were similar to the studies conducted by other research groups. This study will help to understand the amount of friction generated during unconfined compression of brain tissue for strain rates of up to 90/s. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dielectric properties of dog brain tissue measured in vitro across the 0.3-3 GHz band.

PubMed

Mohammed, Beadaa; Bialkowski, Konstanty; Abbosh, Amin; Mills, Paul C; Bradley, Andrew P

2016-09-22

Dielectric properties of dead Greyhound female dogs' brain tissues at different ages were measured at room temperature across the frequency range of 0.3-3 GHz. Measurements were made on excised tissues, in vitro in the laboratory, to carry out dielectric tests on sample tissues. Each dataset for a brain tissue was parametrized using the Cole-Cole expression, and the relevant Cole-Cole parameters for four tissue types are provided. A comparison was made with the database available in literature for other animals and human brain tissue. Results of two types of tissues (white matter and skull) showed systematic variation in dielectric properties as a function of animal age, whereas no significant change related to age was noticed for other tissues. Results provide critical information regarding dielectric properties of animal tissues for a realistic animal head model that can be used to verify the validity and reliability of a microwave head scanner for animals prior to testing on live animals. Bioelectromagnetics. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Brain tissue segmentation based on DTI data

PubMed Central

Liu, Tianming; Li, Hai; Wong, Kelvin; Tarokh, Ashley; Guo, Lei; Wong, Stephen T.C.

2008-01-01

We present a method for automated brain tissue segmentation based on the multi-channel fusion of diffusion tensor imaging (DTI) data. The method is motivated by the evidence that independent tissue segmentation based on DTI parametric images provides complementary information of tissue contrast to the tissue segmentation based on structural MRI data. This has important applications in defining accurate tissue maps when fusing structural data with diffusion data. In the absence of structural data, tissue segmentation based on DTI data provides an alternative means to obtain brain tissue segmentation. Our approach to the tissue segmentation based on DTI data is to classify the brain into two compartments by utilizing the tissue contrast existing in a single channel. Specifically, because the apparent diffusion coefficient (ADC) values in the cerebrospinal fluid (CSF) are more than twice that of gray matter (GM) and white matter (WM), we use ADC images to distinguish CSF and non-CSF tissues. Additionally, fractional anisotropy (FA) images are used to separate WM from non-WM tissues, as highly directional white matter structures have much larger fractional anisotropy values. Moreover, other channels to separate tissue are explored, such as eigenvalues of the tensor, relative anisotropy (RA), and volume ratio (VR). We developed an approach based on the Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm that combines these two-class maps to obtain a complete tissue segmentation map of CSF, GM, and WM. Evaluations are provided to demonstrate the performance of our approach. Experimental results of applying this approach to brain tissue segmentation and deformable registration of DTI data and spoiled gradient-echo (SPGR) data are also provided. PMID:17804258

Accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue.

PubMed

Zhang, Jing; Fan, Yimeng; He, Min; Ma, Xuelei; Song, Yanlin; Liu, Ming; Xu, Jianguo

2017-05-30

Raman spectroscopy could be applied to distinguish tumor from normal tissues. This meta-analysis was conducted to assess the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. PubMed and Embase were searched to identify suitable studies prior to Jan 1st, 2016. We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR), diagnostic odds ratio (DOR), and constructed summary receiver operating characteristics (SROC) curves to identity the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. A total of six studies with 1951 spectra were included. For glioma, the pooled sensitivity and specificity of Raman spectroscopy were 0.96 (95% CI 0.94-0.97) and 0.99 (95% CI 0.98-0.99), respectively. The area under the curve (AUC) was 0.9831. For meningioma, the pooled sensitivity and specificity were 0.98 (95% CI 0.94-1.00) and 1.00 (95% CI 0.98-1.00), respectively. The AUC was 0.9955. This meta-analysis suggested that Raman spectroscopy could be an effective and accurate tool for differentiating glioma and meningioma from normal brain tissue, which would help us both avoid removal of normal tissue and minimize the volume of residual tumor.

The Identification of Aluminum in Human Brain Tissue Using Lumogallion and Fluorescence Microscopy

PubMed Central

Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

2016-01-01

Aluminum in human brain tissue is implicated in the etiologies of neurodegenerative diseases including Alzheimer’s disease. While methods for the accurate and precise measurement of aluminum in human brain tissue are widely acknowledged, the same cannot be said for the visualization of aluminum. Herein we have used transversely-heated graphite furnace atomic absorption spectrometry to measure aluminum in the brain of a donor with Alzheimer’s disease, and we have developed and validated fluorescence microscopy and the fluor lumogallion to show the presence of aluminum in the same tissue. Aluminum is observed as characteristic orange fluorescence that is neither reproduced by other metals nor explained by autofluorescence. This new and relatively simple method to visualize aluminum in human brain tissue should enable more rigorous testing of the aluminum hypothesis of Alzheimer’s disease (and other neurological conditions) in the future. PMID:27472886

Fluoro-Jade and TUNEL staining as useful tools to identify ischemic brain damage following moderate extradural compression of sensorimotor cortex.

PubMed

Kundrotiene, Jurgita; Wägner, Anna; Liljequist, Sture

2004-01-01

Cerebral ischemia was produced by moderate compression for 30 min of a specific brain area in the sensorimotor cortex of Sprague-Dawley rats. On day 1, that is 24 h after the transient sensorimotor compression, ischemia-exposed animals displayed a marked focal neurological deficit documented as impaired beam walking performance. This functional disturbance was mainly due to contralateral fore- and hind-limb paresis. As assessed by daily beam walking tests it was shown that there was a spontaneous recovery of motor functions over a period of five to seven days after the ischemic event. Using histopathological analysis (Nissl staining) we have previously reported that the present experimental paradigm does not produce pannecrosis (tissue cavitation) despite the highly reproducible focal neurological deficit. We now show how staining with fluorescent markers for neuronal death, that is Fluoro-Jade and TUNEL, respectively, identifies regional patterns of selective neuronal death. These observations add further support to the working hypothesis that the brain damage caused by cortical compression-induced ischemia consists of scattered, degenerating neurons in specific brain regions. Postsurgical administration of the AMPA receptor specific antagonist, LY326325 (30 mg/kg; i.p., 70 min after compression), not only improved beam walking performance on day 1 to 3, respectively but also significantly reduced the number of Fluoro-Jade stained neurons on day 5. These results suggest that enhanced AMPA/glutamate receptor activity is at least partially responsible for the ischemia-produced brain damage detected by the fluorescent marker Fluoro-Jade.

Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf

NASA Astrophysics Data System (ADS)

Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; An Nguyen, Thien; Alfano, Robert R.

2014-06-01

Two-photon (2P) excitation of the second singlet (S) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S2 state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf.

PubMed

Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; Nguyen, Thien An; Alfano, Robert R

2014-06-01

Two-photon (2P) excitation of the second singlet (S₂) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S₂ state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S₂ state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

Conformable actively multiplexed high-density surface electrode array for brain interfacing

DOEpatents

Rogers, John; Kim, Dae-Hyeong; Litt, Brian; Viventi, Jonathan

2015-01-13

Provided are methods and devices for interfacing with brain tissue, specifically for monitoring and/or actuation of spatio-temporal electrical waveforms. The device is conformable having a high electrode density and high spatial and temporal resolution. A conformable substrate supports a conformable electronic circuit and a barrier layer. Electrodes are positioned to provide electrical contact with a brain tissue. A controller monitors or actuates the electrodes, thereby interfacing with the brain tissue. In an aspect, methods are provided to monitor or actuate spatio-temporal electrical waveform over large brain surface areas by any of the devices disclosed herein.

Unifying framework for multimodal brain MRI segmentation based on Hidden Markov Chains.

PubMed

Bricq, S; Collet, Ch; Armspach, J P

2008-12-01

In the frame of 3D medical imaging, accurate segmentation of multimodal brain MR images is of interest for many brain disorders. However, due to several factors such as noise, imaging artifacts, intrinsic tissue variation and partial volume effects, tissue classification remains a challenging task. In this paper, we present a unifying framework for unsupervised segmentation of multimodal brain MR images including partial volume effect, bias field correction, and information given by a probabilistic atlas. Here-proposed method takes into account neighborhood information using a Hidden Markov Chain (HMC) model. Due to the limited resolution of imaging devices, voxels may be composed of a mixture of different tissue types, this partial volume effect is included to achieve an accurate segmentation of brain tissues. Instead of assigning each voxel to a single tissue class (i.e., hard classification), we compute the relative amount of each pure tissue class in each voxel (mixture estimation). Further, a bias field estimation step is added to the proposed algorithm to correct intensity inhomogeneities. Furthermore, atlas priors were incorporated using probabilistic brain atlas containing prior expectations about the spatial localization of different tissue classes. This atlas is considered as a complementary sensor and the proposed method is extended to multimodal brain MRI without any user-tunable parameter (unsupervised algorithm). To validate this new unifying framework, we present experimental results on both synthetic and real brain images, for which the ground truth is available. Comparison with other often used techniques demonstrates the accuracy and the robustness of this new Markovian segmentation scheme.

Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

PubMed

Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

2009-01-01

This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

In vivo evaluation of needle force and friction stress during insertion at varying insertion speed into the brain.

PubMed

Casanova, Fernando; Carney, Paul R; Sarntinoranont, Malisa

2014-11-30

Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in tissue damage which can promote flowback along the needle track and improper targeting. The goal of this study was to evaluate friction stress (calculated from needle insertion force) as a measure of tissue contact and damage during needle insertion for varying insertion speeds. Forces and surface dimpling during needle insertion were measured in rat brain in vivo. Needle retraction forces were used to calculate friction stresses. These measures were compared to track damage from a previous study. Differences between brain tissues and soft hydrogels were evaluated for varying insertion speeds: 0.2, 2, and 10mm/s. In brain tissue, average insertion force and surface dimpling increased with increasing insertion speed. Average friction stress along the needle-tissue interface decreased with insertion speed (from 0.58 ± 0.27 to 0.16 ± 0.08 kPa). Friction stress varied between brain regions: cortex (0.227 ± 0.27 kPa), external capsule (0.222 ± 0.19 kPa), and CPu (0.383 ± 0.30 kPa). Hydrogels exhibited opposite trends for dimpling and friction stress with insertion speed. Previously, increasing needle damage with insertion speed has been measured with histological methods. Friction stress appears to decrease with increasing tissue damage and decreasing tissue contact, providing the potential for in vivo and real time evaluation along the needle track. Force derived friction stress decreased with increasing insertion speed and was smaller within white matter regions. Hydrogels exhibited opposite trends to brain tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

Non-invasive intraoperative optical coherence tomography of the resection cavity during surgery of intrinsic brain tumors

NASA Astrophysics Data System (ADS)

Giese, A.; Böhringer, H. J.; Leppert, J.; Kantelhardt, S. R.; Lankenau, E.; Koch, P.; Birngruber, R.; Hüttmann, G.

2006-02-01

Optical coherence tomography (OCT) is a non-invasive imaging technique with a micrometer resolution. It allows non-contact / non-invasive analysis of central nervous system tissues with a penetration depth of 1-3,5 mm reaching a spatial resolution of approximately 4-15 μm. We have adapted spectral-domain OCT (SD-OCT) and time-domain OCT (TD-OCT) for intraoperative detection of residual tumor during brain tumor surgery. Human brain tumor tissue and areas of the resection cavity were analyzed during the resection of gliomas using this new technology. The site of analysis was registered using a neuronavigation system and biopsies were taken and submitted to routine histology. We have used post image acquisition processing to compensate for movements of the brain and to realign A-scan images for calculation of a light attenuation factor. OCT imaging of normal cortex and white matter showed a typical light attenuation profile. Tumor tissue depending on the cellularity of the specimen showed a loss of the normal light attenuation profile resulting in altered light attenuation coefficients compared to normal brain. Based on this parameter and the microstructure of the tumor tissue, which was entirely absent in normal tissue, OCT analysis allowed the discrimination of normal brain tissue, invaded brain, solid tumor tissue, and necrosis. Following macroscopically complete resections OCT analysis of the resection cavity displayed the typical microstructure and light attenuation profile of tumor tissue in some specimens, which in routine histology contained microscopic residual tumor tissue. We have demonstrated that this technology may be applied to the intraoperative detection of residual tumor during resection of human gliomas.

Study of thermal scattering for organic tissues through molecular dynamics

NASA Astrophysics Data System (ADS)

Ramos, Ricardo; Cantargi, Florencia; Marquez Damian, Jose Ignacio; Gonçalves-Carralves, Manuel Sztejnberg

2017-09-01

Boron Neutron Capture Therapy (BNCT) is an experimental therapy for tumors which is based on the nuclear reaction that occurs when 10B is irradiated with thermal neutrons. Calculations for BNCT with Monte Carlo N-Particle (MCNP) take into account the thermal scattering treatment for hydrogen bound in bulk water for any organic tissue. However, in these tissues, hydrogen is also present in macromolecules (protein, lipids, etc.) and in confined water. Thermal scattering cross section for hydrogen in an organic tissue can be determined by calculating the scattering law S(α,β). This function can be obtained with the nuclear data processing system NJOY from the vibrational frequency spectrum of an atom in a molecular system. We performed calculations of the frequency spectrum from molecular dynamics simulations using the program GROMACS. Systems composed of a peptide in a water box were considered, with different proportions of water molecules. All-atom potentials for modeling this molecules were used in order to represent the internal vibrational normal modes for the atoms of hydrogen. The results showed several internal normal modes that in the case of hydrogen bound in bulk water do not appear.

Enhancement of Sexual Behavior in Female Rats by Neonatal Transplantation of Brain Tissue from Males

NASA Astrophysics Data System (ADS)

Arendash, Gary W.; Gorski, Roger A.

1982-09-01

Transplantation of preoptic tissue from male rat neonates into the preoptic area of female littermates increased masculine and feminine sexual behavior in the recipients during adulthood. This suggests that functional connections develop between the transplanted neural tissue and the host brain. A new intraparenchymal brain transplantation technique was used to achieve these results.

Multimodal optical coherence tomography for in vivo imaging of brain tissue structure and microvascular network at glioblastoma

NASA Astrophysics Data System (ADS)

Yashin, Konstantin S.; Kiseleva, Elena B.; Gubarkova, Ekaterina V.; Matveev, Lev A.; Karabut, Maria M.; Elagin, Vadim V.; Sirotkina, Marina A.; Medyanik, Igor A.; Kravets, L. Y.; Gladkova, Natalia D.

2017-02-01

In the case of infiltrative brain tumors the surgeon faces difficulties in determining their boundaries to achieve total resection. The aim of the investigation was to evaluate the performance of multimodal OCT (MM OCT) for differential diagnostics of normal brain tissue and glioma using an experimental model of glioblastoma. The spectral domain OCT device that was used for the study provides simultaneously two modes: cross-polarization and microangiographic OCT. The comparative analysis of the both OCT modalities images from tumorous and normal brain tissue areas concurrently with histologic correlation shows certain difference between when accordingly to morphological and microvascular tissue features.

Influence of strain rate on indentation response of porcine brain.

PubMed

Qian, Long; Zhao, Hongwei; Guo, Yue; Li, Yuanshang; Zhou, Mingxing; Yang, Liguo; Wang, Zhiwei; Sun, Yifan

2018-06-01

Knowledge of brain tissue mechanical properties may be critical for formulating hypotheses about some specific diseases mechanisms and its accurate simulations such as traumatic brain injury (TBI) and tumor growth. Compared to traditional tests (e.g. tensile and compression), indentation shows superiority by virtue of its pinpoint and nondestructive/quasi-nondestructive. As a viscoelastic material, the properties of brain tissue depend on the strain rate by definition. However most efforts focus on the aspect of velocity in the field of brain indentation, rather than strain rate. The influence of strain rate on indentation response of brain tissue is taken little attention. Further, by comparing different results from literatures, it is also obvious that strain rate rather than velocity is more appropriate to characterize mechanical properties of brain. In this paper, to systematically characterize the influence of strain rate, a series of indentation-relaxation tests n = 210) are performed on the cortex of porcine brain using a custom-designed indentation device. The mechanical response that correlates with indenter diameters, depths of indentation and velocities, is revealed for the indentation portion, and elastic behavior of brain tissue is analyzed as the function of strain rate. Similarly, a linear viscoelastic model with a Prony series is employed for the indentation-relaxation portion, wherein the brain tissue shows more viscous and responds more quickly with increasing strain rate. Understanding the effect of strain rate on mechanical properties of brain indentation may be far-reaching for brain injury biomechanics and accurate simulations, but be important for bridging between indentation results of different literatures. Copyright © 2018 Elsevier Ltd. All rights reserved.

Near infrared Raman spectra of human brain lipids

NASA Astrophysics Data System (ADS)

Krafft, Christoph; Neudert, Lars; Simat, Thomas; Salzer, Reiner

2005-05-01

Human brain tissue, in particular white matter, contains high lipid content. These brain lipids can be divided into three principal classes: neutral lipids including the steroid cholesterol, phospholipids and sphingolipids. Major lipids in normal human brain tissue are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, sphingomyelin, galactocerebrosides, gangliosides, sulfatides and cholesterol. Minor lipids are cholesterolester and triacylglycerides. During transformation from normal brain tissue to tumors, composition and concentration of lipids change in a specific way. Therefore, analysis of lipids might be used as a diagnostic parameter to distinguish normal tissue from tumors and to determine the tumor type and tumor grade. Raman spectroscopy has been suggested as an analytical tool to detect these changes even under intra-operative conditions. We recorded Raman spectra of the 12 major and minor brain lipids with 785 nm excitation in order to identify their spectral fingerprints for qualitative and quantitative analyses.

VA's National PTSD Brain Bank: a National Resource for Research.

PubMed

Friedman, Matthew J; Huber, Bertrand R; Brady, Christopher B; Ursano, Robert J; Benedek, David M; Kowall, Neil W; McKee, Ann C

2017-08-25

The National PTSD Brain Bank (NPBB) is a brain tissue biorepository established to support research on the causes, progression, and treatment of PTSD. It is a six-part consortium led by VA's National Center for PTSD with participating sites at VA medical centers in Boston, MA; Durham, NC; Miami, FL; West Haven, CT; and White River Junction, VT along with the Uniformed Services University of Health Sciences. It is also well integrated with VA's Boston-based brain banks that focus on Alzheimer's disease, ALS, chronic traumatic encephalopathy, and other neurological disorders. This article describes the organization and operations of NPBB with specific attention to: tissue acquisition, tissue processing, diagnostic assessment, maintenance of a confidential data biorepository, adherence to ethical standards, governance, accomplishments to date, and future challenges. Established in 2014, NPBB has already acquired and distributed brain tissue to support research on how PTSD affects brain structure and function.

Fingolimod inhibits brain atrophy and promotes brain-derived neurotrophic factor in an animal model of multiple sclerosis.

PubMed

Smith, Paul A; Schmid, Cindy; Zurbruegg, Stefan; Jivkov, Magali; Doelemeyer, Arno; Theil, Diethilde; Dubost, Valérie; Beckmann, Nicolau

2018-05-15

Longitudinal brain atrophy quantification is a critical efficacy measurement in multiple sclerosis (MS) clinical trials and the determination of No Evidence of Disease Activity (NEDA). Utilising fingolimod as a clinically validated therapy we evaluated the use of repeated brain tissue volume measures during chronic experimental autoimmune encephalomyelitis (EAE) as a new preclinical efficacy measure. Brain volume changes were quantified using magnetic resonance imaging (MRI) at 7 Tesla and correlated to treatment-induced brain derived neurotrophic factor (BDNF) measured in blood, cerebrospinal fluid, spinal cord and brain. Serial brain MRI measurements revealed slow progressive brain volume loss in vehicle treated EAE mice despite a stable clinical score. Fingolimod (1 mg/kg) significantly ameliorated brain tissue atrophy in the cerebellum and striatum when administered from established EAE disease onwards. Fingolimod-dependent tissue preservation was associated with induction of BDNF specifically within the brain and co-localized with neuronal soma. In contrast, therapeutic teriflunomide (3 mg/kg) treatment failed to inhibit CNS autoimmune mediated brain degeneration. Finally, weekly anti-IL-17A antibody (15 mg/kg) treatment was highly efficacious and preserved whole brain, cerebellum and striatum volume. Fingolimod-mediated BDNF increases within the CNS may contribute to limiting progressive tissue loss during chronic neuroinflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

In vivo mapping of current density distribution in brain tissues during deep brain stimulation (DBS)

NASA Astrophysics Data System (ADS)

Sajib, Saurav Z. K.; Oh, Tong In; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

2017-01-01

New methods for in vivo mapping of brain responses during deep brain stimulation (DBS) are indispensable to secure clinical applications. Assessment of current density distribution, induced by internally injected currents, may provide an alternative method for understanding the therapeutic effects of electrical stimulation. The current flow and pathway are affected by internal conductivity, and can be imaged using magnetic resonance-based conductivity imaging methods. Magnetic resonance electrical impedance tomography (MREIT) is an imaging method that can enable highly resolved mapping of electromagnetic tissue properties such as current density and conductivity of living tissues. In the current study, we experimentally imaged current density distribution of in vivo canine brains by applying MREIT to electrical stimulation. The current density maps of three canine brains were calculated from the measured magnetic flux density data. The absolute current density values of brain tissues, including gray matter, white matter, and cerebrospinal fluid were compared to assess the active regions during DBS. The resulting current density in different tissue types may provide useful information about current pathways and volume activation for adjusting surgical planning and understanding the therapeutic effects of DBS.

Effects of positive end-expiratory pressure on brain tissue oxygen pressure of severe traumatic brain injury patients with acute respiratory distress syndrome: A pilot study.

PubMed

Nemer, Sérgio Nogueira; Caldeira, Jefferson B; Santos, Ricardo G; Guimarães, Bruno L; Garcia, João Márcio; Prado, Darwin; Silva, Ricardo T; Azeredo, Leandro M; Faria, Eduardo R; Souza, Paulo Cesar P

2015-12-01

To verify whether high positive end-expiratory pressure levels can increase brain tissue oxygen pressure, and also their effects on pulse oxygen saturation, intracranial pressure, and cerebral perfusion pressure. Twenty traumatic brain injury patients with acute respiratory distress syndrome were submitted to positive end-expiratory pressure levels of 5, 10, and 15 cm H2O progressively. The 3 positive end-expiratory pressure levels were used during 20 minutes for each one, whereas brain tissue oxygen pressure, oxygen saturation, intracranial pressure, and cerebral perfusion pressure were recorded. Brain tissue oxygen pressure and oxygen saturation increased significantly with increasing positive end-expiratory pressure from 5 to 10 and from 10 to 15 cm H2O (P=.0001 and P=.0001 respectively). Intracranial pressure and cerebral perfusion pressure did not differ significantly with increasing positive end-expiratory pressure from 5 to 10 and from 10 to 15 cm H2O (P=.16 and P=.79 respectively). High positive end-expiratory pressure levels increased brain tissue oxygen pressure and oxygen saturation, without increase in intracranial pressure or decrease in cerebral perfusion pressure. High positive end-expiratory pressure levels can be used in severe traumatic brain injury patients with acute respiratory distress syndrome as a safe alternative to improve brain oxygenation. Copyright © 2015 Elsevier Inc. All rights reserved.

Pharmacokinetics and brain penetration of carbapenems in mice.

PubMed

Matsumoto, Kazuaki; Kurihara, Yuji; Kuroda, Yuko; Hori, Seiji; Kizu, Junko

2016-05-01

An adverse effect associated with the administration of carbapenems is central nervous system (CNS) toxicity, with higher brain concentrations of carbapenems being linked to an increased risk of seizures. However, the pharmacokinetics and brain penetration of carbapenems have not yet been examined. Thus, the aim of this in vivo investigation was to determine the pharmacokinetics and brain penetration of carbapenems in mice. Blood samples and brain tissue samples were obtained 10, 20, 30, 60, and 120 min after the subcutaneous administration of carbapenems (91 mg/kg). We obtained the following values for the pharmacokinetic parameters of carbapenems in mice: 1.20-1.71 L/h/kg for CLtotal/F, 1.41-2.03 h(-1) for Ke, 0.34-0.51 h for T1/2, 0.66-0.95 L/kg for Vss/F, 0.49-0.73 h for MRT, 83.46-110.58 μg/mL for Cmax, plasma, and 0.28-0.83 μg/g for Cmax, brain tissue. The AUC0-∞ of the carbapenems tested in plasma were in the following order: doripenem > meropenem > biapenem > imipenem, and in brain tissue were: imipenem > doripenem > meropenem > biapenem. The degrees of brain tissue penetration, defined as the AUC0-∞, brain tissue/fAUC0-∞, plasma ratio, were 0.016 for imipenem, 0.004 for meropenem, 0.002 for biapenem, and 0.008 for doripenem. The results of the present study demonstrated that, of the carbapenems examined, imipenem penetrated brain tissue to the greatest extent. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research.

PubMed

Walton, Esther; Hass, Johanna; Liu, Jingyu; Roffman, Joshua L; Bernardoni, Fabio; Roessner, Veit; Kirsch, Matthias; Schackert, Gabriele; Calhoun, Vince; Ehrlich, Stefan

2016-03-01

Given the difficulty of procuring human brain tissue, a key question in molecular psychiatry concerns the extent to which epigenetic signatures measured in more accessible tissues such as blood can serve as a surrogate marker for the brain. Here, we aimed (1) to investigate the blood-brain correspondence of DNA methylation using a within-subject design and (2) to identify changes in DNA methylation of brain-related biological pathways in schizophrenia.We obtained paired blood and temporal lobe biopsy samples simultaneously from 12 epilepsy patients during neurosurgical treatment. Using the Infinium 450K methylation array we calculated similarity of blood and brain DNA methylation for each individual separately. We applied our findings by performing gene set enrichment analyses (GSEA) of peripheral blood DNA methylation data (Infinium 27K) of 111 schizophrenia patients and 122 healthy controls and included only Cytosine-phosphate-Guanine (CpG) sites that were significantly correlated across tissues.Only 7.9% of CpG sites showed a statistically significant, large correlation between blood and brain tissue, a proportion that although small was significantly greater than predicted by chance. GSEA analysis of schizophrenia data revealed altered methylation profiles in pathways related to precursor metabolites and signaling peptides.Our findings indicate that most DNA methylation markers in peripheral blood do not reliably predict brain DNA methylation status. However, a subset of peripheral data may proxy methylation status of brain tissue. Restricting the analysis to these markers can identify meaningful epigenetic differences in schizophrenia and potentially other brain disorders. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Predicting Intracranial Pressure and Brain Tissue Oxygen Crises in Patients With Severe Traumatic Brain Injury.

PubMed

Myers, Risa B; Lazaridis, Christos; Jermaine, Christopher M; Robertson, Claudia S; Rusin, Craig G

2016-09-01

To develop computer algorithms that can recognize physiologic patterns in traumatic brain injury patients that occur in advance of intracranial pressure and partial brain tissue oxygenation crises. The automated early detection of crisis precursors can provide clinicians with time to intervene in order to prevent or mitigate secondary brain injury. A retrospective study was conducted from prospectively collected physiologic data. intracranial pressure, and partial brain tissue oxygenation crisis events were defined as intracranial pressure of greater than or equal to 20 mm Hg lasting at least 15 minutes and partial brain tissue oxygenation value of less than 10 mm Hg for at least 10 minutes, respectively. The physiologic data preceding each crisis event were used to identify precursors associated with crisis onset. Multivariate classification models were applied to recorded data in 30-minute epochs of time to predict crises between 15 and 360 minutes in the future. The neurosurgical unit of Ben Taub Hospital (Houston, TX). Our cohort consisted of 817 subjects with severe traumatic brain injury. Our algorithm can predict the onset of intracranial pressure crises with 30-minute advance warning with an area under the receiver operating characteristic curve of 0.86 using only intracranial pressure measurements and time since last crisis. An analogous algorithm can predict the start of partial brain tissue oxygenation crises with 30-minute advanced warning with an area under the receiver operating characteristic curve of 0.91. Our algorithms provide accurate and timely predictions of intracranial hypertension and tissue hypoxia crises in patients with severe traumatic brain injury. Almost all of the information needed to predict the onset of these events is contained within the signal of interest and the time since last crisis.

Detection of Human Brain Cancer Infiltration ex vivo and in vivo Using Quantitative Optical Coherence Tomography*

PubMed Central

Kut, Carmen; Chaichana, Kaisorn L.; Xi, Jiefeng; Raza, Shaan M.; Ye, Xiaobu; McVeigh, Elliot R.; Rodriguez, Fausto J.; Quinones-Hinojosa, Alfredo; Li, Xingde

2015-01-01

More complete brain cancer resection can prolong survival and delay recurrence. However, it is challenging to distinguish cancer from non-cancer tissues intraoperatively, especially at the transitional, infiltrative zones. This is especially critical in eloquent regions (e.g. speech and motor areas). This study tested the feasibility of label-free, quantitative optical coherence tomography (OCT) for differentiating cancer from non-cancer in human brain tissues. Fresh ex vivo human brain tissues were obtained from 32 patients with grades II-IV brain cancer and 5 patients with non-cancer brain pathologies. Based on volumetric OCT imaging data, pathologically confirmed brain cancer tissues (both high-grade and low-grade) had significantly lower optical attenuation values at both cancer core and infiltrated zones when compared with non-cancer white matter, and OCT achieved high sensitivity and specificity at an attenuation threshold of 5.5 mm-1 for brain cancer patients. We also used this attenuation threshold to confirm the intraoperative feasibility of performing in vivo OCT-guided surgery using a murine model harboring human brain cancer. Our OCT system was capable of processing and displaying a color-coded optical property map in real time at a rate of 110-215 frames per second, or 1.2-2.4 seconds for an 8-16 mm3 tissue volume, thus providing direct visual cues for cancer versus non-cancer areas. Our study demonstrates the translational and practical potential of OCT in differentiating cancer from non-cancer tissue. Its intraoperative use may facilitate safe and extensive resection of infiltrative brain cancers and consequently lead to improved outcomes when compared with current clinical standards. PMID:26084803

Surface-enhanced Raman scattering of rat tissues.

PubMed

Aydin, Omer; Kahraman, Mehmet; Kiliç, Ertuğul; Culha, Mustafa

2009-06-01

Surface-enhanced Raman scattering (SERS) is proven to be a powerful tool for investigation of biological structures. In this study, tissues obtained from different rat organs are examined using SERS. The tissue samples are crushed with a pestle after sudden freezing in liquid nitrogen and mixed with a concentrated colloidal silver nanoparticle suspension. The reproducibility of SERS spectra acquired from several tissue samples from different organs is demonstrated. The collected spectra are comparatively evaluated based on the physiological function of the organ from which the tissue is obtained. The spectra from the tissues show significant differences and indicate that they can be used for tissue characterization and differentiation. The identification of the origins of the bands on the spectra is also attempted. This study suggests that SERS can be used to monitor the changes at the molecular level during metabolic changes in an organ or tissue as a result of a disease or another cause.

Biocompatible near-infrared fluorescent nanoparticles for macro and microscopic in vivo functional bioimaging

PubMed Central

Chu, Liliang; Wang, Shaowei; Li, Kanghui; Xi, Wang; Zhao, Xinyuan; Qian, Jun

2014-01-01

Near-infrared (NIR) imaging technology has been widely used for biomedical research and applications, since it can achieve deep penetration in biological tissues due to less absorption and scattering of NIR light. In our research, polymer nanoparticles with NIR fluorophores doped were synthesized. The morphology, absorption/emission features and chemical stability of the fluorescent nanoparticles were characterized, separately. NIR fluorescent nanoparticles were then utilized as bright optical probes for macro in vivo imaging of mice, including sentinel lymph node (SLN) mapping, as well as distribution and excretion monitoring of nanoparticles in animal body. Furthermore, we applied the NIR fluorescent nanoparticles in in vivo microscopic bioimaging via a confocal microscope. Under the 635 nm-CW excitation, the blood vessel architecture in the ear and the brain of mice, which were administered with nanoparticles, was visualized very clearly. The imaging depth of our one-photon microscopy, which was assisted with NIR fluorescent nanoprobes, can reach as deep as 500 μm. Our experiments show that NIR fluorescent nanoparticles have great potentials in various deep-tissue imaging applications. PMID:25426331

Tomographic imaging of bone composition using coherently scattered x rays

NASA Astrophysics Data System (ADS)

Batchelar, Deidre L.; Dabrowski, W.; Cunningham, Ian A.

2000-04-01

Bone tissue consists primarily of calcium hydroxyapatite crystals (bone mineral) and collagen fibrils. Bone mineral density (BMD) is commonly used as an indicator of bone health. Techniques available at present for assessing bone health provide a measure of BMD, but do not provide information about the degree of mineralization of the bone tissue. This may be adequate for assessing diseases in which the collagen-mineral ratio remains constant, as assumed in osteoporosis, but is insufficient when the mineralization state is known to change, as in osteomalacia. No tool exists for the in situ examination of collagen and hydroxyapatite density distributions independently. Coherent-scatter computed tomography (CSCT) is a technique we are developing that produces images of the low- angle scatter properties of tissue. These depend on the molecular structure of the scatterer making it possible to produce material-specific maps of each component in a conglomerate. After corrections to compensate for exposure fluctuations, self-attenuation of scatter and the temporal response of the image intensifier, material-specific images of mineral, collagen, fat and water distributions are obtained. The gray-level in these images provides the volumetric density of each component independently.

Light scattering of semitransparent sintered polytetrafluoroethylene films.

PubMed

Li, Qinghe; Lee, Bong Jae; Zhang, Zhuomin M; Allen, David W

2008-01-01

Polytetrafluoroethylene (PTFE) is a strongly scattering material and has been regarded to have optical properties similar to biological tissues. In the present study, the bidirectional reflectance distribution function (BRDF) and the bidirectional transmittance distribution function (BTDF) of several PTFE films, with thicknesses from 0.11 to 10 mm, are measured using a laser scatterometer at the wavelength of 635 nm. The directional-hemispherical reflectance (R) and transmittance (T) were obtained by integrating BRDF and BTDF for normal incidence. Comparison of the ratio of the measured R and T with that calculated from the adding-doubling method allows the determination of the reduced scattering coefficient. Furthermore, the effect of surface scattering is investigated by measuring the polarization-dependent BRDF and BTDF at oblique incidence. By analyzing the measurement uncertainty of BTDF in the near-normal observation angles at normal incidence, the present authors found that the scattering coefficient of PTFE should exceed 1200 cm(-1), which is much greater than that of biological tissues. On the other hand, the absorption coefficient of PTFE must be less than 0.01 cm(-1), much smaller than that of biological tissues, a necessary condition to achieve R > or =0.98 with a 10-mm-thick slab.

Quantification of tissue oxygenation levels using diffuse reflectance spectroscopy

NASA Astrophysics Data System (ADS)

B. S., Suresh Anand; N., Sujatha

2011-08-01

Tumor growth is characterized by increased metabolic activity. The light absorption profile of hemoglobin in dysplastic tissue is different from a normal tissue. Neovascularization is a hallmark of many diseases and can serve as a predictive biomarker for the detection of cancers. Spectroscopic techniques can provide information about the metabolic and morphological changes related to the progression of neoplasia. Diffuse reflectance spectroscopy (DRS) measures the absorption and scattering properties of a biological tissue and this method can provide clinically useful information for the early diagnosis of epithelial precancers. We used tissue simulating phantoms with absorbing and scattering molecules for the determination of total hemoglobin concentration, hemoglobin oxygen saturation and intensity difference between the deoxy and oxy hemoglobin bands. The results show promising approach for the differentiating normal and malignant states of a tissue.

Extracellular Nucleotides in Exercise: Possible Effect on Brain Metabolism.

ERIC Educational Resources Information Center

Forrester, Tom

1979-01-01

A review of experiments which demonstrate the release of ATP from skeletal muscle, cardiac muscle, and active brain tissue. Effects of exogenously applied ATP to brain tissue are discussed in relation to whole body exercise. (Author/SA)

A spatiotemporal atlas of MR intensity, tissue probability and shape of the fetal brain with application to segmentation

PubMed Central

Habas, Piotr A.; Kim, Kio; Corbett-Detig, James M.; Rousseau, Francois; Glenn, Orit A.; Barkovich, A. James; Studholme, Colin

2010-01-01

Modeling and analysis of MR images of the developing human brain is a challenge due to rapid changes in brain morphology and morphometry. We present an approach to the construction of a spatiotemporal atlas of the fetal brain with temporal models of MR intensity, tissue probability and shape changes. This spatiotemporal model is created from a set of reconstructed MR images of fetal subjects with different gestational ages. Groupwise registration of manual segmentations and voxelwise nonlinear modeling allow us to capture the appearance, disappearance and spatial variation of brain structures over time. Applying this model to atlas-based segmentation, we generate age-specific MR templates and tissue probability maps and use them to initialize automatic tissue delineation in new MR images. The choice of model parameters and the final performance are evaluated using clinical MR scans of young fetuses with gestational ages ranging from 20.57 to 24.71 weeks. Experimental results indicate that quadratic temporal models can correctly capture growth-related changes in the fetal brain anatomy and provide improvement in accuracy of atlas-based tissue segmentation. PMID:20600970

Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

PubMed

Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian

2017-06-22

Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Silver nanoparticles (AgNPs) as a contrast agent for imaging of animal tissue using swept-source optical coherence tomography (SSOCT)

NASA Astrophysics Data System (ADS)

Mondal, Indranil; Raj, Shipra; Roy, Poulomi; Poddar, Raju

2018-01-01

We present noninvasive three-dimensional depth-resolved imaging of animal tissue with a swept-source optical coherence tomography system at 1064 nm center wavelength and silver nanoparticles (AgNPs) as a potential contrast agent. A swept-source laser light source is used to enable an imaging rate of 100 kHz (100 000 A-scans s-1). Swept-source optical coherence tomography is a new variant of the optical coherence tomography (OCT) technique, offering unique advantages in terms of sensitivity, reduction of motion artifacts, etc. To enhance the contrast of an OCT image, AgNPs are utilized as an exogeneous contrast agent. AgNPs are synthesized using a modified Tollens method and characterization is done by UV-vis spectroscopy, dynamic light scattering, scanning electron microscopy and energy dispersive x-ray spectroscopy. In vitro imaging of chicken breast tissue, with and without the application of AgNPs, is performed. The effect of AgNPs is studied with different exposure times. A mathematical model is also built to calculate changes in the local scattering coefficient of tissue from OCT images. A quantitative estimation of scattering coefficient and contrast is performed for tissues with and without application of AgNPs. Significant improvement in contrast and increase in scattering coefficient with time is observed.

Heat generation and light scattering of green fluorescent protein-like pigments in coral tissue

NASA Astrophysics Data System (ADS)

Lyndby, Niclas H.; Kühl, Michael; Wangpraseurt, Daniel

2016-05-01

Green fluorescent protein (GFP)-like pigments have been proposed to have beneficial effects on coral photobiology. Here, we investigated the relationships between green fluorescence, coral heating and tissue optics for the massive coral Dipsastraea sp. (previously Favia sp.). We used microsensors to measure tissue scalar irradiance and temperature along with hyperspectral imaging and combined imaging of variable chlorophyll fluorescence and green fluorescence. Green fluorescence correlated positively with coral heating and scalar irradiance enhancement at the tissue surface. Coral tissue heating saturated for maximal levels of green fluorescence. The action spectrum of coral surface heating revealed that heating was highest under red (peaking at 680 nm) irradiance. Scalar irradiance enhancement in coral tissue was highest when illuminated with blue light, but up to 62% (for the case of highest green fluorescence) of this photon enhancement was due to green fluorescence emission. We suggest that GFP-like pigments scatter the incident radiation, which enhances light absorption and heating of the coral. However, heating saturates, because intense light scattering reduces the vertical penetration depth through the tissue eventually leading to reduced light absorption at high fluorescent pigment density. We conclude that fluorescent pigments can have a central role in modulating coral light absorption and heating.

A New Modeling for the Changes in the Distribution of Scatterers in Cirrhotic Liver

NASA Astrophysics Data System (ADS)

Hara, Takashi; Hachiya, Hiroyuki

2000-05-01

The human liver is composed of small hexagonal structures called liver lobules. Cirrhosis destroys these liver lobules and replaces them with permanent connective tissue referred to as regenerative nodules. In this paper, we propose a new modeling technique for changes in the scatterer distribution in liver tissue considering the structure of liver lobules to obtain images of the cirrhotic liver over continuous stages. Using these images, we analyze the relationship between changes in characteristics of biological tissue and changes in B-mode images during progressive liver cirrhosis.

In vitro terahertz spectroscopy of gelatin-embedded human brain tumors: a pilot study

NASA Astrophysics Data System (ADS)

Chernomyrdin, N. V.; Gavdush, A. A.; Beshplav, S.-I. T.; Malakhov, K. M.; Kucheryavenko, A. S.; Katyba, G. M.; Dolganova, I. N.; Goryaynov, S. A.; Karasik, V. E.; Spektor, I. E.; Kurlov, V. N.; Yurchenko, S. O.; Komandin, G. A.; Potapov, A. A.; Tuchin, V. V.; Zaytsev, K. I.

2018-04-01

We have performed the in vitro terahertz (THz) spectroscopy of human brain tumors. In order to fix tissues for the THz measurements, we have applied the gelatin embedding. It allows for preserving tissues from hydration/dehydration and sustaining their THz response similar to that of the freshly-excised tissues for a long time after resection. We have assembled an experimental setup for the reflection-mode measurements of human brain tissues based on the THz pulsed spectrometer. We have used this setup to study in vitro the refractive index and the amplitude absorption coefficient of 2 samples of malignant glioma (grade IV), 1 sample of meningioma (grade I), and samples of intact tissues. We have observed significant differences between the THz responses of normal and pathological tissues of the brain. The results of this paper highlight the potential of the THz technology in the intraoperative neurodiagnosis of tumors relying on the endogenous labels of tumorous tissues.

Gene expression profiles help identify the tissue of origin for metastatic brain cancers.

PubMed

Wu, Alan H B; Drees, Julia C; Wang, Hangpin; VandenBerg, Scott R; Lal, Anita; Henner, William D; Pillai, Raji

2010-04-26

Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases. This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

PubMed Central

2010-01-01

Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers. PMID:20420692

Physics-based subsurface visualization of human tissue.

PubMed

Sharp, Richard; Adams, Jacob; Machiraju, Raghu; Lee, Robert; Crane, Robert

2007-01-01

In this paper, we present a framework for simulating light transport in three-dimensional tissue with inhomogeneous scattering properties. Our approach employs a computational model to simulate light scattering in tissue through the finite element solution of the diffusion equation. Although our model handles both visible and nonvisible wavelengths, we especially focus on the interaction of near infrared (NIR) light with tissue. Since most human tissue is permeable to NIR light, tools to noninvasively image tumors, blood vasculature, and monitor blood oxygenation levels are being constructed. We apply this model to a numerical phantom to visually reproduce the images generated by these real-world tools. Therefore, in addition to enabling inverse design of detector instruments, our computational tools produce physically-accurate visualizations of subsurface structures.

Full scattering profile for detecting physiological tissue properties

NASA Astrophysics Data System (ADS)

Duadi, Hamootal; Fixler, Dror

2017-02-01

Light reflectance and transmission from soft tissue has been utilized in noninvasive clinical measurement devices such as the photoplethysmograph (PPG) and reflectance pulse oximeter. Most methods of near infrared (NIR) spectroscopy focus on the volume reflectance from a semi-infinite sample, while very few measure transmission. We have previously shown that examining the full scattering profile (FSP), which is the angular distribution of exiting photons, provides more comprehensive information when measuring from a cylindrical tissue, such as earlobe, fingertip and pinched tissue. Our hypothesis is that the change in blood vessel diameter is more significant than the change in optical properties. The findings of this work demonstrate a realistic model for optical tissue measurements such as NIR spectroscopy, PPG and pulse oximetery.

Feasibility of Small Animal Anatomical and Functional Imaging with Neutrons: A Monte Carlo Simulation Study

NASA Astrophysics Data System (ADS)

Medich, David C.; Currier, Blake H.; Karellas, Andrew

2014-10-01

A novel technique is presented for obtaining a single in-vivo image containing both functional and anatomical information in a small animal model such as a mouse. This technique, which incorporates appropriate image neutron-scatter rejection and uses a neutron opaque contrast agent, is based on neutron radiographic technology and was demonstrated through a series of Monte Carlo simulations. With respect to functional imaging, this technique can be useful in biomedical and biological research because it could achieve a spatial resolution orders of magnitude better than what presently can be achieved with current functional imaging technologies such as nuclear medicine (PET, SPECT) and fMRI. For these studies, Monte Carlo simulations were performed with thermal (0.025 eV) neutrons in a 3 cm thick phantom using the MCNP5 simulations software. The goals of these studies were to determine: 1) the extent that scattered neutrons degrade image contrast; 2) the contrasts of various normal and diseased tissues under conditions of complete scatter rejection; 3) the concentrations of Boron-10 and Gadolinium-157 required for contrast differentiation in functional imaging; and 4) the efficacy of collimation for neutron scatter image rejection. Results demonstrate that with proper neutron-scatter rejection, a neutron fluence of 2 ×107 n/cm2 will provide a signal to noise ratio of at least one ( S/N ≥ 1) when attempting to image various 300 μm thick tissues placed in a 3 cm thick phantom. Similarly, a neutron fluence of only 1 ×107 n/cm2 is required to differentiate a 300 μm thick diseased tissue relative to its normal tissue counterpart. The utility of a B-10 contrast agent was demonstrated at a concentration of 50 μg/g to achieve S/N ≥ 1 in 0.3 mm thick tissues while Gd-157 requires only slightly more than 10 μg/g to achieve the same level of differentiation. Lastly, neutron collimator with an L/D ratio from 50 to 200 were calculated to provide appropriate scatter rejection for thick tissue biological imaging with neutrons.

Effect of baculovirus P35 protein on apoptosis in brain tissue of rats with acute cerebral infarction.

PubMed

Ji, J F; Ma, X H

2015-08-10

We explored the effect of baculovirus P35 protein on apoptosis in the brain tissue of rats with acute cerebral infarction (ACI). A rat model of middle cerebral artery infarction was created. The rats were randomly divided into sham, model, and treatment groups. Baculovirus P35 protein was injected into the intracranial arteries of the treatment group rats. The rats in the model group were given an equal volume of phosphate-buffered saline. The rats were sacrificed after 72 h and the brain tissue was separated. The levels of caspase-3, Bcl-2, and Bax mRNA, the brain cell apoptosis index, and the infarct size were determined. After 72 h, the levels of caspase-3 and Bax mRNA in the model and treatment groups were significantly greater than in the sham group, and the levels of Bcl-2 mRNA were significantly smaller (P < 0.05). The levels of caspase-3 and Bax mRNA were significantly lower in the treatment group than in the model group, and the level of Bcl-2 mRNA was significantly greater (P < 0.05). Compared with the sham group, the brain tissue apoptosis index and the cerebral infarction area increased significantly in the model and treatment groups (P < 0.05). The brain tissue apoptosis index and cerebral infarction area in the treatment group were significantly lower than in the model group (P < 0.05). Baculovirus P35 protein can effectively inhibit brain cell apoptosis in rats with ACI. It delayed apoptosis and necrosis in subjects with ACI tissue and had a protective effect on brain tissue.

Quantitative assessment of brain tissue oxygenation in porcine models of cardiac arrest and cardiopulmonary resuscitation using hyperspectral near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Lotfabadi, Shahin S.; Toronov, Vladislav; Ramadeen, Andrew; Hu, Xudong; Kim, Siwook; Dorian, Paul; Hare, Gregory M. T.

2014-03-01

Near-infrared spectroscopy (NIRS) is a non-invasive tool to measure real-time tissue oxygenation in the brain. In an invasive animal experiment we were able to directly compare non-invasive NIRS measurements on the skull with invasive measurements directly on the brain dura matter. We used a broad-band, continuous-wave hyper-spectral approach to measure tissue oxygenation in the brain of pigs under the conditions of cardiac arrest, cardiopulmonary resuscitation (CPR), and defibrillation. An additional purpose of this research was to find a correlation between mortality due to cardiac arrest and inadequacy of the tissue perfusion during attempts at resuscitation. Using this technique we measured the changes in concentrations of oxy-hemoglobin [HbO2] and deoxy-hemoglobin [HHb] to quantify the tissue oxygenation in the brain. We also extracted cytochrome c oxidase changes Δ[Cyt-Ox] under the same conditions to determine increase or decrease in cerebral oxygen delivery. In this paper we proved that applying CPR, [HbO2] concentration and tissue oxygenation in the brain increase while [HHb] concentration decreases which was not possible using other measurement techniques. We also discovered a similar trend in changes of both [Cyt-Ox] concentration and tissue oxygen saturation (StO2). Both invasive and non-invasive measurements showed similar results.

Multimodality instrument for tissue characterization

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

2004-01-01

A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration. The use of this system will make surgical procedures safer, more accurate, and more efficient. Other applications of this system include the detection, prognosis and treatment of breast cancer, prostate cancer, spinal diseases, and use in general exploratory surgery.

MO-F-CAMPUS-I-03: Tissue Equivalent Material Phantom to Test and Optimize Coherent Scatter Imaging for Tumor Classification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albanese, K; Morris, R; Lakshmanan, M

Purpose: To accurately model different breast geometries using a tissue equivalent phantom, and to classify these tissues in a coherent x-ray scatter imaging system. Methods: A breast phantom has been designed to assess the capability of coded aperture coherent x-ray scatter imaging system to classify different types of breast tissue (adipose, fibroglandular, tumor). The tissue-equivalent phantom was modeled as a hollow plastic cylinder containing multiple cylindrical and spherical inserts that can be positioned, rearranged, or removed to model different breast geometries. Each enclosure can be filled with a tissue-equivalent material and excised human tumors. In this study, beef and lard,more » placed inside 2-mm diameter plastic Nalgene containers, were used as surrogates for fibroglandular and adipose tissue, respectively. The phantom was imaged at 125 kVp, 40 mA for 10 seconds each with a 1-mm pencil beam. The raw data were reconstructed using a model-based reconstruction algorithm and yielded the location and form factor, or momentum transfer (q) spectrum of the materials that were imaged. The measured material form factors were then compared to the ground truth measurements acquired by x-ray diffraction (XRD) imaging. Results: The tissue equivalent phantom was found to accurately model different types of breast tissue by qualitatively comparing our measured form factors to those of adipose and fibroglandular tissue from literature. Our imaging system has been able to define the location and composition of the various materials in the phantom. Conclusion: This work introduces a new tissue equivalent phantom for testing and optimization of our coherent scatter imaging system for material classification. In future studies, the phantom will enable the use of a variety of materials including excised human tissue specimens in evaluating and optimizing our imaging system using pencil- and fan-beam geometries. United States Department of Homeland Security Duke University Medical Center - Department of Radiology Carl E Ravin Advanced Imaging Laboratories Duke University Medical Physics Graduate Program.« less

Therapeutic Ultrasound Enhancement of Drug Delivery to Soft Tissues

NASA Astrophysics Data System (ADS)

Lewis, George; Wang, Peng; Lewis, George; Olbricht, William

2009-04-01

Effects of exposure to 1.58 MHz focused ultrasound on transport of Evans Blue Dye (EBD) in soft tissues are investigated when an external pressure gradient is applied to induce convective flow through the tissue. The magnitude of the external pressure gradient is chosen to simulate conditions in brain parenchyma during convection-enhanced drug delivery (CED) to the brain. EBD uptake and transport are measured in equine brain, avian muscle and agarose brain-mimicking phantoms. Results show that ultrasound enhances EBD uptake and transport, and the greatest enhancement occurs when the external pressure gradient is applied. The results suggest that exposure of the brain parenchyma to ultrasound could enhance penetration of material infused into the brain during CED therapy.

Development of an experimental model of brain tissue heterotopia in the lung

PubMed Central

Quemelo, Paulo Roberto Veiga; Sbragia, Lourenço; Peres, Luiz Cesar

2007-01-01

Summary The presence of heterotopic brain tissue in the lung is a rare abnormality. The cases reported thus far are usually associated with neural tube defects (NTD). As there are no reports of experimental models of NTD that present this abnormality, the objective of the present study was to develop a surgical method of brain tissue heterotopia in the lung. We used 24 pregnant Swiss mice divided into two groups of 12 animals each, denoted 17GD and 18GD according to the gestational day (GD) when caesarean section was performed to collect the fetuses. Surgery was performed on the 15th GD, one fetus was removed by hysterectomy and its brain tissue was cut into small fragments and implanted in the lung of its litter mates. Thirty-four live fetuses were obtained from the 17GD group. Of these, eight (23.5%) were used as control (C), eight (23.5%) were sham operated (S) and 18 (52.9%) were used for pulmonary brain tissue implantation (PBI). Thirty live fetuses were obtained from the females of the 18GD group. Of these, eight (26.6%) were C, eight (26.6%) S and 14 (46.6%) were used for PBI. Histological examination of the fetal trunks showed implantation of GFAP-positive brain tissue in 85% of the fetuses of the 17GD group and in 100% of those of the 18GD group, with no significant difference between groups for any of the parameters analysed. The experimental model proved to be efficient and of relatively simple execution, showing complete integration of the brain tissue with pulmonary and pleural tissue and thus representing a model that will permit the study of different aspects of cell implantation and interaction. PMID:17877535

Biochemical Fractionation and Stable Isotope Dilution Liquid Chromatography-mass Spectrometry for Targeted and Microdomain-specific Protein Quantification in Human Postmortem Brain Tissue*

PubMed Central

MacDonald, Matthew L.; Ciccimaro, Eugene; Prakash, Amol; Banerjee, Anamika; Seeholzer, Steven H.; Blair, Ian A.; Hahn, Chang-Gyu

2012-01-01

Synaptic architecture and its adaptive changes require numerous molecular events that are both highly ordered and complex. A majority of neuropsychiatric illnesses are complex trait disorders, in which multiple etiologic factors converge at the synapse via many signaling pathways. Investigating the protein composition of synaptic microdomains from human patient brain tissues will yield valuable insights into the interactions of risk genes in many disorders. These types of studies in postmortem tissues have been limited by the lack of proper study paradigms. Thus, it is necessary not only to develop strategies to quantify protein and post-translational modifications at the synapse, but also to rigorously validate them for use in postmortem human brain tissues. In this study we describe the development of a liquid chromatography-selected reaction monitoring method, using a stable isotope-labeled neuronal proteome standard prepared from the brain tissue of a stable isotope-labeled mouse, for the multiplexed quantification of target synaptic proteins in mammalian samples. Additionally, we report the use of this method to validate a biochemical approach for the preparation of synaptic microdomain enrichments from human postmortem prefrontal cortex. Our data demonstrate that a targeted mass spectrometry approach with a true neuronal proteome standard facilitates accurate and precise quantification of over 100 synaptic proteins in mammalian samples, with the potential to quantify over 1000 proteins. Using this method, we found that protein enrichments in subcellular fractions prepared from human postmortem brain tissue were strikingly similar to those prepared from fresh mouse brain tissue. These findings demonstrate that biochemical fractionation methods paired with targeted proteomic strategies can be used in human brain tissues, with important implications for the study of neuropsychiatric disease. PMID:22942359

Cranial irradiation increases tumor growth in experimental breast cancer brain metastasis.

PubMed

Hamilton, Amanda M; Wong, Suzanne M; Wong, Eugene; Foster, Paula J

2018-05-01

Whole-brain radiotherapy is the standard of care for patients with breast cancer with multiple brain metastases and, although this treatment has been essential in the management of existing brain tumors, there are many known negative consequences associated with the irradiation of normal brain tissue. In our study, we used in vivo magnetic resonance imaging analysis to investigate the influence of radiotherapy-induced damage of healthy brain on the arrest and growth of metastatic breast cancer cells in a mouse model of breast cancer brain metastasis. We observed that irradiated, but otherwise healthy, neural tissue had an increased propensity to support metastatic growth compared with never-irradiated controls. The elucidation of the impact of irradiation on normal neural tissue could have implications in clinical patient management, particularly in patients with residual systemic disease or with residual radio-resistant brain cancer. Copyright © 2018 John Wiley & Sons, Ltd.

Optical narrow band frequency analysis of polystyrene bead mixtures

NASA Astrophysics Data System (ADS)

Popov, Kaloyan A.; Kurzweg, Timothy P.

2010-02-01

Early pre-cancerous conditions in tissue can be studied as mixture of cancerous and healthy cells. White light spectroscopy is a promising technique for determining the size of scattering elements, which, in cells are the nuclei. However, in a mixture of different sized scatterers, possibly between healthy and cancerous cells, the white light spectroscopy spatial data is not easily analyzed, making it difficult to determine the individual components that comprise the mixture. We have previously found by obtaining spatial limited data by using an optical filter and converting this spatial data into the Fourier domain, we can determine characteristic signature frequencies for individual scatterers. In this paper, we show analysis of phantom tissues representing esophagus tissue. We examine phantom tissue representing pre-cancerous conditions, when some of the cell nuclei increase in size. We also experimentally show a relationship between the particle concentration and the amplitude of the Fourier signature peak. In addition, we discuss the frequency peak amplitude dependency based on the Tyndall Effect, which describes particles aggregating into clusters.

Effects of acupuncture on tissue oxygenation of the rat brain.

PubMed

Chen, G S; Erdmann, W

1978-04-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by smypathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture points (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible and was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase in inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes increased brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients.

Development of a portable frequency-domain angle-resolved low coherence interferometry system

NASA Astrophysics Data System (ADS)

Pyhtila, John W.; Wax, Adam

2007-02-01

Improved methods for detecting dysplasia, or pre-cancerous growth, are a current clinical need. Random biopsy and subsequent diagnosis through histological analysis is the current gold standard in endoscopic surveillance for dysplasia. However, this approach only allows limited examination of the at-risk tissue and has the drawback of a long delay in time-to-diagnosis. In contrast, optical scattering spectroscopy methods offer the potential to assess cellular structure and organization in vivo, thus allowing for instantaneous diagnosis and increased coverage of the at-risk tissue. Angle-resolved low coherence interferometry (a/LCI), a novel scattering spectroscopy technique, combines the ability of low-coherence interferometry to isolate scattered light from sub-surface tissue layers with the ability of light scattering spectroscopy to obtain structural information on sub-wavelength scales, specifically by analyzing the angular distribution of the backscattered light. In application to examining tissue, a/LCI enables depthresolved quantitative measurements of changes in the size and texture of cell nuclei, which are characteristic biomarkers of dysplasia. The capabilities of a/LCI were demonstrated initially by detecting pre-cancerous changes in epithelial cells within intact, unprocessed, animal tissues. Recently, we have developed a new frequency-domain a/LCI system, with sub-second acquisition time and a novel fiber optic probe. Preliminary results using the fa/LCI system to examine human esophageal tissue in Barrett's esophagus patients demonstrate the clinical viability of the approach. In this paper, we present a new portable system which improves upon the design of the fa/LCI system to allow for higher quality data to be collected in the clinic. Accurate sizing of polystyrene microspheres and cell nuclei from ex vivo human esophageal tissue is presented. These results demonstrate the promise of a/LCI as a clinically viable diagnostic tool.

Metals in tissues of migrant semipalmated sandpipers (Calidris pusilla) from Delaware Bay, New Jersey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burger, Joanna, E-mail: burger@biology.rutgers.edu; Environmental and Occupational Health Sciences Institute; Gochfeld, Michael

2014-08-15

There is an abundance of field data on levels of metals for feathers in a variety of birds, but relatively few data for tissues, especially for migrant species from one location. In this paper we examine the levels of arsenic, cadmium, chromium, lead, manganese, mercury and selenium in muscle, liver, brain, fat and breast feathers from migrant semipalmated sandpipers (Calidris pusilla) collected from Delaware Bay, New Jersey. Our primary objectives were to (1) examine variation as a function of tissue, (2) determine the relationship of metal levels among tissues, and (3) determine the selenium:mercury molar ratio in different tissues sincemore » selenium is thought to protect against mercury toxicity. We were also interested in whether the large physiological changes that occur while shorebirds are on Delaware Bay (e.g. large weight gains in 2–3 weeks) affected metal levels, especially in the brain. There were significant differences among tissues for all metals. The brain had the lowest levels of arsenic and cadmium, and was tied for the lowest levels of all other metals except lead and selenium. Correlations among metals in tissues were varied, with mercury levels being positively correlated for muscle and brain, and for liver and breast feathers. Weights vary among individuals at the Delaware Bay stopover, as they arrive light, and gain weight prior to migration north. Bird weight and levels of arsenic, cadmium, and selenium in the brain were negatively correlated, while they were positively correlated for lead. There was no positive correlation for mercury in the brain as a function of body weight. The selenium:mercury molar ratio varied significantly among tissues, with brain (ratio of 141) and fat having the highest ratios, and liver and breast feathers having the lowest. In all cases, the ratio was above 21, suggesting the potential for amelioration of mercury toxicity. - Highlights: • Metal levels were examined for migrant semipalmated sandpipers. • There were differences in metal levels among internal tissues. • Brain had the lowest levels of arsenic and cadmium. • Bird weight and arsenic, cadmium, and selenium levels in brain were negatively correlated. • Selenium:mercury molar ratio varied among tissues (21–141, suggesting protection)« less

Compression stiffening of brain and its effect on mechanosensing by glioma cells

NASA Astrophysics Data System (ADS)

Pogoda, Katarzyna; Chin, LiKang; Georges, Penelope C.; Byfield, FitzRoy J.; Bucki, Robert; Kim, Richard; Weaver, Michael; Wells, Rebecca G.; Marcinkiewicz, Cezary; Janmey, Paul A.

2014-07-01

Many cell types, including neurons, astrocytes and other cells of the central nervous system, respond to changes in the extracellular matrix or substrate viscoelasticity, and increased tissue stiffness is a hallmark of several disease states, including fibrosis and some types of cancers. Whether the malignant tissue in brain, an organ that lacks the protein-based filamentous extracellular matrix of other organs, exhibits the same macroscopic stiffening characteristic of breast, colon, pancreatic and other tumors is not known. In this study we show that glioma cells, like normal astrocytes, respond strongly in vitro to substrate stiffness in the range of 100 to 2000 Pa, but that macroscopic (mm to cm) tissue samples isolated from human glioma tumors have elastic moduli in the order of 200 Pa that are indistinguishable from those of normal brain. However, both normal brain and glioma tissues increase their shear elastic moduli under modest uniaxial compression, and glioma tissue stiffens more strongly under compression than normal brain. These findings suggest that local tissue stiffness has the potential to alter glial cell function, and that stiffness changes in brain tumors might arise not from increased deposition or crosslinking of the collagen-rich extracellular matrix, but from pressure gradients that form within the tumors in vivo.

Mary Jane Hogue (1883-1962): A pioneer in human brain tissue culture.

PubMed

Zottoli, Steven J; Seyfarth, Ernst-August

2018-05-16

The ability to maintain human brain explants in tissue culture was a critical step in the use of these cells for the study of central nervous system disorders. Ross G. Harrison (1870-1959) was the first to successfully maintain frog medullary tissue in culture in 1907, but it took another 38 years before successful culture of human brain tissue was accomplished. One of the pioneers in this achievement was Mary Jane Hogue (1883-1962). Hogue was born into a Quaker family in 1883 in West Chester, Pennsylvania, and received her undergraduate degree from Goucher College in Baltimore, Maryland. Research with the developmental biologist Theodor Boveri (1862-1915) in Würzburg, Germany, resulted in her Ph.D. (1909). Hogue transitioned from studying protozoa to the culture of human brain tissue in the 1940s and 1950s, when she was one of the first to culture cells from human fetal, infant, and adult brain explants. We review Hogue's pioneering contributions to the study of human brain cells in culture, her putative identification of progenitor neuroblast and/or glioblast cells, and her use of the cultures to study the cytopathogenic effects of poliovirus. We also put Hogue's work in perspective by discussing how other women pioneers in tissue culture influenced Hogue and her research.

Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering

PubMed Central

Mourant, Judith R.; Bocklage, Thérese J.; Powers, Tamara M.; Greene, Heather M.; Dorin, Maxine H.; Waxman, Alan G.; Zsemlye, Meggan M.; Smith, Harriet O.

2009-01-01

Objective To examine the utility of in vivo elastic light scattering measurements to identify cervical intraepithelial neoplasias (CIN) 2/3 and cancers in women undergoing colposcopy and to determine the effects of patient characteristics such as menstrual status on the elastic light scattering spectroscopic measurements. Materials and Methods A fiber optic probe was used to measure light transport in the cervical epithelium of patients undergoing colposcopy. Spectroscopic results from 151 patients were compared with histopathology of the measured and biopsied sites. A method of classifying the measured sites into two clinically relevant categories was developed and tested using five-fold cross-validation. Results Statistically significant effects by age at diagnosis, menopausal status, timing of the menstrual cycle, and oral contraceptive use were identified, and adjustments based upon these measurements were incorporated in the classification algorithm. A sensitivity of 77±5% and a specificity of 62±2% were obtained for separating CIN 2/3 and cancer from other pathologies and normal tissue. Conclusions The effects of both menstrual status and age should be taken into account in the algorithm for classifying tissue sites based on elastic light scattering spectroscopy. When this is done, elastic light scattering spectroscopy shows good potential for real-time diagnosis of cervical tissue at colposcopy. Guiding biopsy location is one potential near-term clinical application area, while facilitating ”see and treat” protocols is a longer term goal. Improvements in accuracy are essential. PMID:20694193

Measuring the reduced scattering coefficient and γ with SFR spectroscopy: studying the phase function dependence (Conference Presentation)

NASA Astrophysics Data System (ADS)

Post, Anouk L.; Zhang, Xu; Bosschaart, Nienke; Van Leeuwen, Ton G.; Sterenborg, Henricus J. C. M.; Faber, Dirk J.

2016-03-01

Both Optical Coherence Tomography (OCT) and Single Fiber Reflectance Spectroscopy (SFR) are used to determine various optical properties of tissue. We developed a method combining these two techniques to measure the scattering anisotropy (g1) and γ (=1-g2/1-g1), related to the 1st and 2nd order moments of the phase function. The phase function is intimately associated with the cellular organization and ultrastructure of tissue, physical parameters that may change during disease onset and progression. Quantification of these parameters may therefore allow for improved non-invasive, in vivo discrimination between healthy and diseased tissue. With SFR the reduced scattering coefficient and γ can be extracted from the reflectance spectrum (Kanick et al., Biomedical Optics Express 2(6), 2011). With OCT the scattering coefficient can be extracted from the signal as a function of depth (Faber et al., Optics Express 12(19), 2004). Consequently, by combining SFR and OCT measurements at the same wavelengths, the scattering anisotropy (g) can be resolved using µs'= µs*(1-g). We performed measurements on a suspension of silica spheres as a proof of principle. The SFR model for the reflectance as a function of the reduced scattering coefficient and γ is based on semi-empirical modelling. These models feature Monte-Carlo (MC) based model constants. The validity of these constants - and thus the accuracy of the estimated parameters - depends on the phase function employed in the MC simulations. Since the phase function is not known when measuring in tissue, we will investigate the influence of assuming an incorrect phase function on the accuracy of the derived parameters.

Using white-light spectroscopy for size determination of tissue phantoms

NASA Astrophysics Data System (ADS)

Vitol, Elina A.; Kurzweg, Timothy P.; Nabet, Bahram

2005-09-01

Along with breast and cervical cancer, esophageal adenocarcinoma is one of the most common types of cancers. The characteristic features of pre-cancerous tissues are the increase in cell proliferation rate and cell nuclei enlargement, which both take place in the epithelium of human body surfaces. However, in the early stages of cancer these changes are very small and difficult to detect, even for expert pathologists. The aim of our research is to develop an optical probe for in vivo detection of nuclear size changes using white light scattering from cell nuclei. The probe will be employed through an endoscope and will be used for the medical examination of the esophagus. The proposed method of examination will be noninvasive, cheap, and specific, compared to a biopsy. Before the construction of this probe, we have developed theory to determine the nuclei size from the reflection data. In this first stage of our research, we compare experimental and theoretical scattered light intensities. Our theoretical model includes the values of scatterer size from which we can extract the nuclei size value. We first performed the study of polystyrene microspheres, acting as a tissue phantom. Spectral and angular distributions of scattered white light from tissue phantoms were studied. Experimental results show significant differences between the spectra of microspheres of different sizes and demonstrate almost linear relation between the number of spectral oscillations and the size of microspheres. Best results were achieved when the scattered light spectrum was collected at 30° to the normal of the sample surface. We present these research results in this paper. In ongoing work, normal and cancerous mammalian cell studies are being performed in order to determine cell nuclei size correlation with the size of microspheres through the light scattering spectrum observation.

Mimicking brain tissue binding in an in vitro model of the blood-brain barrier illustrates differences between in vitro and in vivo methods for assessing the rate of brain penetration.

PubMed

Heymans, Marjolein; Sevin, Emmanuel; Gosselet, Fabien; Lundquist, Stefan; Culot, Maxime

2018-06-01

Assessing the rate of drug delivery to the central nervous system (CNS) in vitro has been used for decades to predict whether CNS drug candidates are likely to attain their pharmacological targets, located within the brain parenchyma, at an effective dose. The predictive value of in vitro blood-brain barrier (BBB) models is therefore frequently assessed by comparing in vitro BBB permeability, usually quoted as the endothelial permeability coefficient (P e ) or apparent permeability (P app ), to their rate of BBB permeation measured in vivo, the latter being commonly assessed in rodents. In collaboration with AstraZeneca (DMPK department, Södertälje, Sweden), the in vitro BBB permeability (P app and P e ) of 27 marketed CNS drugs has been determined using a bovine in vitro BBB model and compared to their in vivo permeability (P vivo ), obtained by rat in-situ brain perfusion. The latter was taken from published data from Summerfield et al. (2007). This comparison confirmed previous reports, showing a strong in vitro/in vivo correlation for hydrophilic compounds, characterized by low brain tissue binding and a weak correlation for lipophilic compounds, characterized by high brain tissue binding. This observation can be explained by the influence of brain tissue binding on the uptake of drugs into the CNS in vivo and the absence of possible brain tissue binding in vitro. The use of glial cells (GC) in the in vitro BBB model to mimic brain tissue binding and the introduction of a new calculation method for in vitro BBB permeability (P vitro ) resulted in a strong correlation between the in vitro and in vivo rate of BBB permeation for the whole set of compounds. These findings might facilitate further in vitro to in vivo extrapolation for CNS drug candidates. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Development and Validation of a Method for Alcohol Analysis in Brain Tissue by Headspace Gas Chromatography with Flame Ionization Detector

PubMed Central

Chun, Hao-Jung; Poklis, Justin L.; Poklis, Alphonse; Wolf, Carl E.

2016-01-01

Ethanol is the most widely used and abused drug. While blood is the preferred specimen for analysis, tissue specimens such as brain serve as alternative specimens for alcohol analysis in post-mortem cases where blood is unavailable or contaminated. A method was developed using headspace gas chromatography with flame ionization detection (HS-GC-FID) for the detection and quantification of ethanol, acetone, isopropanol, methanol and n-propanol in brain tissue specimens. Unfixed volatile-free brain tissue specimens were obtained from the Department of Pathology at Virginia Commonwealth University. Calibrators and controls were prepared from 4-fold diluted homogenates of these brain tissue specimens, and were analyzed using t-butanol as the internal standard. The chromatographic separation was performed with a Restek BAC2 column. A linear calibration was generated for all analytes (mean r2 > 0.9992) with the limits of detection and quantification of 100–110 mg/kg. Matrix effect from the brain tissue was determined by comparing the slopes of matrix prepared calibration curves with those of aqueous calibration curves; no significant differences were observed for ethanol, acetone, isopropanol, methanol and n-propanol. The bias and the CVs for all volatile controls were ≤10%. The method was also evaluated for carryover, selectivity, interferences, bench-top stability and freeze-thaw stability. The HS-GC-FID method was determined to be reliable and robust for the analysis of ethanol, acetone, isopropanol, methanol and n-propanol concentrations in brain tissue, effectively expanding the specimen options for post-mortem alcohol analysis. PMID:27488829

Hyper- and viscoelastic modeling of needle and brain tissue interaction.

PubMed

Lehocky, Craig A; Yixing Shi; Riviere, Cameron N

2014-01-01

Deep needle insertion into brain is important for both diagnostic and therapeutic clinical interventions. We have developed an automated system for robotically steering flexible needles within the brain to improve targeting accuracy. In this work, we have developed a finite element needle-tissue interaction model that allows for the investigation of safe parameters for needle steering. The tissue model implemented contains both hyperelastic and viscoelastic properties to simulate the instantaneous and time-dependent responses of brain tissue. Several needle models were developed with varying parameters to study the effects of the parameters on tissue stress, strain and strain rate during needle insertion and rotation. The parameters varied include needle radius, bevel angle, bevel tip fillet radius, insertion speed, and rotation speed. The results will guide the design of safe needle tips and control systems for intracerebral needle steering.

Numerical analysis of the diffusive mass transport in brain tissues with applications to optical sensors

NASA Astrophysics Data System (ADS)

Neculae, Adrian P.; Otte, Andreas; Curticapean, Dan

2013-03-01

In the brain-cell microenvironment, diffusion plays an important role: apart from delivering glucose and oxygen from the vascular system to brain cells, it also moves informational substances between cells. The brain is an extremely complex structure of interwoven, intercommunicating cells, but recent theoretical and experimental works showed that the classical laws of diffusion, cast in the framework of porous media theory, can deliver an accurate quantitative description of the way molecules are transported through this tissue. The mathematical modeling and the numerical simulations are successfully applied in the investigation of diffusion processes in tissues, replacing the costly laboratory investigations. Nevertheless, modeling must rely on highly accurate information regarding the main parameters (tortuosity, volume fraction) which characterize the tissue, obtained by structural and functional imaging. The usual techniques to measure the diffusion mechanism in brain tissue are the radiotracer method, the real time iontophoretic method and integrative optical imaging using fluorescence microscopy. A promising technique for obtaining the values for characteristic parameters of the transport equation is the direct optical investigation using optical fibers. The analysis of these parameters also reveals how the local geometry of the brain changes with time or under pathological conditions. This paper presents a set of computations concerning the mass transport inside the brain tissue, for different types of cells. By measuring the time evolution of the concentration profile of an injected substance and using suitable fitting procedures, the main parameters characterizing the tissue can be determined. This type of analysis could be an important tool in understanding the functional mechanisms of effective drug delivery in complex structures such as the brain tissue. It also offers possibilities to realize optical imaging methods for in vitro and in vivo measurements using optical fibers. The model also may help in radiotracer biomarker models for the understanding of the mechanism of action of new chemical entities.

The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage.

PubMed

Stiefel, Michael F; Heuer, Gregory G; Abrahams, John M; Bloom, Stephanie; Smith, Michelle J; Maloney-Wilensky, Eileen; Grady, M Sean; LeRoux, Peter D

2004-10-01

Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.

Advantages of analyzing postmortem brain samples in routine forensic drug screening-Case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD).

PubMed

Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar; Linnet, Kristian

2017-09-01

Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34-10.8μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration levels. The cause of death in case 1 was collision-induced brain injury, while it was drowning in case 2 and 3 and thus not drug intoxication. However, the toxicological findings could help explain the decedent's inability to cope with brain injury or drowning incidents. The presented findings could help establish reference concentrations in brain samples and assist in interpretation of results from forensic drug screening in brain tissue. This is to the author's knowledge the first report of LSD, iso-LSD, and oxo-HO-LSD measured in brain tissue samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting therapeutics across the blood brain barrier (BBB), prerequisite towards thrombolytic therapy for cerebrovascular disorders-an overview and advancements.

PubMed

Pulicherla, K K; Verma, Mahendra Kumar

2015-04-01

Cerebral tissues possess highly selective and dynamic protection known as blood brain barrier (BBB) that regulates brain homeostasis and provides protection against invading pathogens and various chemicals including drug molecules. Such natural protection strictly monitors entry of drug molecules often required for the management of several diseases and disorders including cerebral vascular and neurological disorders. However, in recent times, the ischemic cerebrovascular disease and clinical manifestation of acute arterial thrombosis are the most common causes of mortality and morbidity worldwide. The management of cerebral Ischemia requires immediate infusion of external thrombolytic into systemic circulation and must cross the blood brain barrier. The major challenge with available thrombolytic is their poor affinity towards the blood brain barrier and cerebral tissue subsequently. In the clinical practice, a high dose of thrombolytic often prescribed to deliver drugs across the blood brain barrier which results in drug dependent toxicity leading to damage of neuronal tissues. In recent times, more emphasis was given to utilize blood brain barrier transport mechanism to deliver drugs in neuronal tissue. The blood brain barrier expresses a series of receptor on membrane became an ideal target for selective drug delivery. In this review, the author has given more emphasis molecular biology of receptor on blood brain barrier and their potential as a carrier for drug molecules to cerebral tissues. Further, the use of nanoscale design and real-time monitoring for developed therapeutic to encounter drug dependent toxicity has been reviewed in this study.

Better diet quality relates to larger brain tissue volumes: The Rotterdam Study.

PubMed

Croll, Pauline H; Voortman, Trudy; Ikram, M Arfan; Franco, Oscar H; Schoufour, Josje D; Bos, Daniel; Vernooij, Meike W

2018-05-16

To investigate the relation of diet quality with structural brain tissue volumes and focal vascular lesions in a dementia-free population. From the population-based Rotterdam Study, 4,447 participants underwent dietary assessment and brain MRI scanning between 2005 and 2015. We excluded participants with an implausible energy intake, prevalent dementia, or cortical infarcts, leaving 4,213 participants for the current analysis. A diet quality score (0-14) was calculated reflecting adherence to Dutch dietary guidelines. Brain MRI was performed to obtain information on brain tissue volumes, white matter lesion volume, lacunes, and cerebral microbleeds. The associations of diet quality score and separate food groups with brain structures were assessed using multivariable linear and logistic regression. We found that better diet quality related to larger brain volume, gray matter volume, white matter volume, and hippocampal volume. Diet quality was not associated with white matter lesion volume, lacunes, or microbleeds. High intake of vegetables, fruit, whole grains, nuts, dairy, and fish and low intake of sugar-containing beverages were associated with larger brain volumes. A better diet quality is associated with larger brain tissue volumes. These results suggest that the effect of nutrition on neurodegeneration may act via brain structure. More research, in particular longitudinal research, is needed to unravel direct vs indirect effects between diet quality and brain health. © 2018 American Academy of Neurology.

Permeabilization of brain tissue in situ enables multiregion analysis of mitochondrial function in a single mouse brain.

PubMed

Herbst, Eric A F; Holloway, Graham P

2015-02-15

Mitochondrial function in the brain is traditionally assessed through analysing respiration in isolated mitochondria, a technique that possesses significant tissue and time requirements while also disrupting the cooperative mitochondrial reticulum. We permeabilized brain tissue in situ to permit analysis of mitochondrial respiration with the native mitochondrial morphology intact, removing the need for isolation time and minimizing tissue requirements to ∼2 mg wet weight. The permeabilized brain technique was validated against the traditional method of isolated mitochondria and was then further applied to assess regional variation in the mouse brain with ischaemia-reperfusion injuries. A transgenic mouse model overexpressing catalase within mitochondria was applied to show the contribution of mitochondrial reactive oxygen species to ischaemia-reperfusion injuries in different brain regions. This technique enhances the accessibility of addressing physiological questions in small brain regions and in applying transgenic mouse models to assess mechanisms regulating mitochondrial function in health and disease. Mitochondria function as the core energy providers in the brain and symptoms of neurodegenerative diseases are often attributed to their dysregulation. Assessing mitochondrial function is classically performed in isolated mitochondria; however, this process requires significant isolation time, demand for abundant tissue and disruption of the cooperative mitochondrial reticulum, all of which reduce reliability when attempting to assess in vivo mitochondrial bioenergetics. Here we introduce a method that advances the assessment of mitochondrial respiration in the brain by permeabilizing existing brain tissue to grant direct access to the mitochondrial reticulum in situ. The permeabilized brain preparation allows for instant analysis of mitochondrial function with unaltered mitochondrial morphology using significantly small sample sizes (∼2 mg), which permits the analysis of mitochondrial function in multiple subregions within a single mouse brain. Here this technique was applied to assess regional variation in brain mitochondrial function with acute ischaemia-reperfusion injuries and to determine the role of reactive oxygen species in exacerbating dysfunction through the application of a transgenic mouse model overexpressing catalase within mitochondria. Through creating accessibility to small regions for the investigation of mitochondrial function, the permeabilized brain preparation enhances the capacity for examining regional differences in mitochondrial regulation within the brain, as the majority of genetic models used for unique approaches exist in the mouse model. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Expression profiles of inhibitor of growth protein 2 in normal and cancer tissues: An immunohistochemical screening analysis.

PubMed

Zhao, Shuang; Yang, Xue-Feng; Gou, Wen-Feng; Lu, Hang; Li, Hua; Zhu, Zhi-Tu; Sun, Hong-Zhi; Zheng, Hua-Chuan

2016-02-01

Inhibitor of growth protein 2 (ING2) has an important role in the regulation of chromatin remodeling, cell proliferation, cell‑cycle arrest, senescence and apoptosis. The present study performed an immunohistochemical analysis for expression profiling of ING2 protein in an array of tissues comprising normal mouse and human tissues, as well as human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung (n=192) carcinoma tissues. In mouse tissues, ING2 was detected in the nuclei and cytoplasm of the glandular epithelium of breast, hepatocytes, intestine, bronchium and alveoli, as well as the squamous epithelium of skin and glomeruli, and in myocardial cells, while it was located in the cytoplasm of renal tubules and striated muscle cells. ING2 protein was scattered in the brain and spleen. In human tissues, ING2 protein was principally distributed in the cytoplasm, while in it was present in the cytoplasm and nuclei in the stomach, intestine, cervix, endometrium trachea, breast and pancreas. The nuclear location of ING2 in the stomach was more prominent than that in the cytoplasm. High ING2 immunoreactivity was detected in the tongue, stomach, skin, pancreas, cervix and breast, whereas weakly in the brain stem, thymus, thyroid, lung, striated muscle, testis, bladder and ovary. In total, 617 out of 1,194 of the tested cancer tissues (51.7%) were ING2-positive. In most cases, ING2 expression was found to be restricted to the cytoplasm of all cancer tissues, while in certain cancer types, including renal clear cell, ovarian and colorectal carcinoma, it was occasionally present in the nuclei. Among the cancer tissues examined, ING2 was most frequently expressed in breast cancer (67.4%) and gynecological cancer types, including ovarian cancer (61.5%) and endometrial cancer (57.3%). Compared with that in the respective normal tissues, ING2 expression in breast cancer tissues was decreased, while that in cervical cancer was upregulated in the nuclei as well as the cytoplasm. In endometrial cancer, expression of ING2 was increased in the nuclei and declined in the cytoplasm compared with that in the normal endometrium. ING2‑positive cases were less frequent for renal clear cell carcinoma (17.7%). The results of the present study suggested that ING2 may be involved in the repair and regeneration of organs or tissues and is associated with breast and gynecological carcinogenesis.

Simulation of a fast diffuse optical tomography system based on radiative transfer equation

NASA Astrophysics Data System (ADS)

Motevalli, S. M.; Payani, A.

2016-12-01

Studies show that near-infrared (NIR) light (light with wavelength between 700nm and 1300nm) undergoes two interactions, absorption and scattering, when it penetrates a tissue. Since scattering is the predominant interaction, the calculation of light distribution in the tissue and the image reconstruction of absorption and scattering coefficients are very complicated. Some analytical and numerical methods, such as radiative transport equation and Monte Carlo method, have been used for the simulation of light penetration in tissue. Recently, some investigators in the world have tried to develop a diffuse optical tomography system. In these systems, NIR light penetrates the tissue and passes through the tissue. Then, light exiting the tissue is measured by NIR detectors placed around the tissue. These data are collected from all the detectors and transferred to the computational parts (including hardware and software), which make a cross-sectional image of the tissue after performing some computational processes. In this paper, the results of the simulation of an optical diffuse tomography system are presented. This simulation involves two stages: a) Simulation of the forward problem (or light penetration in the tissue), which is performed by solving the diffusion approximation equation in the stationary state using FEM. b) Simulation of the inverse problem (or image reconstruction), which is performed by the optimization algorithm called Broyden quasi-Newton. This method of image reconstruction is faster compared to the other Newton-based optimization algorithms, such as the Levenberg-Marquardt one.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated networkmore » (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.« less

Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis.

PubMed

Yan, Kun; Fu, Zongming; Yang, Chen; Zhang, Kai; Jiang, Shanshan; Lee, Dong-Hoon; Heo, Hye-Young; Zhang, Yi; Cole, Robert N; Van Eyk, Jennifer E; Zhou, Jinyuan

2015-08-01

To investigate the biochemical origin of the amide photon transfer (APT)-weighted hyperintensity in brain tumors. Seven 9 L gliosarcoma-bearing rats were imaged at 4.7 T. Tumor and normal brain tissue samples of equal volumes were prepared with a coronal rat brain matrix and a tissue biopsy punch. The total tissue protein and the cytosolic subproteome were extracted from both samples. Protein samples were analyzed using two-dimensional gel electrophoresis, and the proteins with significant abundance changes were identified by mass spectrometry. There was a significant increase in the cytosolic protein concentration in the tumor, compared to normal brain regions, but the total protein concentrations were comparable. The protein profiles of the tumor and normal brain tissue differed significantly. Six cytosolic proteins, four endoplasmic reticulum proteins, and five secreted proteins were considerably upregulated in the tumor. Our experiments confirmed an increase in the cytosolic protein concentration in tumors and identified several key proteins that may cause APT-weighted hyperintensity.

Dexamethasone increases production of C-type natriuretic peptide in the sheep brain.

PubMed

Wilson, Michele O; McNeill, Bryony A; Barrell, Graham K; Prickett, Timothy C R; Espiner, Eric A

2017-10-01

Although C-type natriuretic peptide (CNP) has high abundance in brain tissues and cerebrospinal fluid (CSF), the source and possible factors regulating its secretion within the central nervous system (CNS) are unknown. Here we report the dynamic effects of a single IV bolus of dexamethasone or saline solution on plasma, CSF, CNS and pituitary tissue content of CNP products in adult sheep, along with changes in CNP gene expression in selected tissues. Both CNP and NTproCNP (the amino-terminal product of proCNP) in plasma and CSF showed dose-responsive increases lasting 12-16 h after dexamethasone, whereas other natriuretic peptides were unaffected. CNS tissue concentrations of CNP and NTproCNP were increased by dexamethasone in all of the 12 regions examined. Abundance was highest in limbic tissues, pons and medulla oblongata. Relative to controls, CNP gene expression ( NPPC ) was upregulated by dexamethasone in 5 of 7 brain tissues examined. Patterns of responses differed in pituitary tissue. Whereas the abundance of CNP in both lobes of the pituitary gland greatly exceeded that of brain tissues, neither CNP nor NTproCNP concentration was affected by dexamethasone, despite an increase in NPPC expression. This is the first report of enhanced production and secretion of CNP in brain tissues in response to a corticosteroid. Activation of CNP secretion within CNS tissues by dexamethasone, not exhibited by other natriuretic peptides, suggests an important role for CNP in settings of acute stress. Differential findings in pituitary tissues likely relate to altered processing of proCNP storage and secretion. © 2017 Society for Endocrinology.

Optical properties of human colon tissues in the 350 – 2500 nm spectral range

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bashkatov, A N; Genina, E A; Kochubey, V I

2014-08-31

We present the optical characteristics of the mucosa and submucosa of human colon tissue. The experiments are performed in vitro using a LAMBDA 950 spectrophotometer in the 350 – 2500 nm spectral range. The absorption and scattering coefficients and the scattering anisotropy factor are calculated based on the measured diffuse reflectance and total and collimated transmittance spectra using the inverse Monte Carlo method. (laser biophotonics)

Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

PubMed Central

Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang

2014-01-01

Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue. PMID:25368644

Sub-diffusive scattering parameter maps recovered using wide-field high-frequency structured light imaging.

PubMed

Kanick, Stephen Chad; McClatchy, David M; Krishnaswamy, Venkataramanan; Elliott, Jonathan T; Paulsen, Keith D; Pogue, Brian W

2014-10-01

This study investigates the hypothesis that structured light reflectance imaging with high spatial frequency patterns [Formula: see text] can be used to quantitatively map the anisotropic scattering phase function distribution [Formula: see text] in turbid media. Monte Carlo simulations were used in part to establish a semi-empirical model of demodulated reflectance ([Formula: see text]) in terms of dimensionless scattering [Formula: see text] and [Formula: see text], a metric of the first two moments of the [Formula: see text] distribution. Experiments completed in tissue-simulating phantoms showed that simultaneous analysis of [Formula: see text] spectra sampled at multiple [Formula: see text] in the frequency range [0.05-0.5] [Formula: see text] allowed accurate estimation of both [Formula: see text] in the relevant tissue range [0.4-1.8] [Formula: see text], and [Formula: see text] in the range [1.4-1.75]. Pilot measurements of a healthy volunteer exhibited [Formula: see text]-based contrast between scar tissue and surrounding normal skin, which was not as apparent in wide field diffuse imaging. These results represent the first wide-field maps to quantify sub-diffuse scattering parameters, which are sensitive to sub-microscopic tissue structures and composition, and therefore, offer potential for fast diagnostic imaging of ultrastructure on a size scale that is relevant to surgical applications.

MEASUREMENT OF SMALL MECHANICAL VIBRATIONS OF BRAIN TISSUE EXPOSED TO EXTREMELY-LOW-FREQUENCY ELECTRIC FIELDS

EPA Science Inventory

Electromagnetic fields can interact with biological tissue both electrically and mechanically. This study investigated the mechanical interaction between brain tissue and an extremely-low-frequency (ELF) electric field by measuring the resultant vibrational amplitude. The exposur...

Physiological and pathological clinical conditions and light scattering in brain

NASA Astrophysics Data System (ADS)

Kurata, Tsuyoshi; Iwata, Sachiko; Tsuda, Kennosuke; Kinoshita, Masahiro; Saikusa, Mamoru; Hara, Naoko; Oda, Motoki; Ohmae, Etsuko; Araki, Yuko; Sugioka, Takashi; Takashima, Sachio; Iwata, Osuke

2016-08-01

MRI of preterm infants at term commonly reveals subtle brain lesions such as diffuse white matter injury, which are linked with later cognitive impairments. The timing and mechanism of such injury remains unclear. The reduced scattering coefficient of near-infrared light (μs’) has been shown to correlate linearly with gestational age in neonates. To identify clinical variables associated with brain μs’, 60 preterm and full-term infants were studied within 7 days of birth. Dependence of μs’ obtained from the frontal head on clinical variables was assessed. In the univariate analysis, smaller μs’ was associated with antenatal glucocorticoid, emergency Caesarean section, requirement for mechanical ventilation, smaller gestational age, smaller body sizes, low 1- and 5-minute Apgar scores, higher cord blood pH and PO2, and higher blood HCO3- at the time of study. Multivariate analysis revealed that smaller gestational age, requirement for mechanical ventilation, and higher HCO3- at the time of study were correlated with smaller μs’. Brain μs’ depended on variables associated with physiological maturation and pathological conditions of the brain. Further longitudinal studies may help identify pathological events and clinical conditions responsible for subtle brain injury and subsequent cognitive impairments following preterm birth.

The adult brain tissue response to hollow fiber membranes of varying surface architecture with or without cotransplanted cells

NASA Astrophysics Data System (ADS)

Zhang, Ning

A variety of biomaterials have been chronically implanted into the central nervous system (CNS) for repair or therapeutic purposes. Regardless of the application, chronic implantation of materials into the CNS induces injury and elicits a wound healing response, eventually leading to the formation of a dense extracellular matrix (ECM)-rich scar tissue that is associated with the segregation of implanted materials from the surrounding normal tissue. Often this reaction results in impaired performance of indwelling CNS devices. In order to enhance the performance of biomaterial-based implantable devices in the CNS, this thesis investigated whether adult brain tissue response to implanted biomaterials could be manipulated by changing biomaterial surface properties or further by utilizing the biology of co-transplanted cells. Specifically, the adult rat brain tissue response to chronically implanted poly(acrylonitrile-vinylchloride) (PAN-PVC) hollow fiber membranes (HFMs) of varying surface architecture were examined temporally at 2, 4, and 12 weeks postimplantation. Significant differences were discovered in the brain tissue response to the PAN-PVC HFMs of varying surface architecture at 4 and 12 weeks. To extend this work, whether the soluble factors derived from a co-transplanted cellular component further affect the brain tissue response to an implanted HFM in a significant way was critically exploited. The cells used were astrocytes, whose ability to influence scar formation process following CNS injury by physical contact with the host tissue had been documented in the literature. Data indicated for the first time that astrocyte-derived soluble factors ameliorate the adult brain tissue reactivity toward HFM implants in an age-dependent manner. While immature astrocytes secreted soluble factors that suppressed the brain tissue reactivity around the implants, mature astrocytes secreted factors that enhanced the gliotic response. These findings prove the feasibility of ameliorating the CNS tissue reactivity toward biomaterials implants by varying biomaterial surface properties or incorporating scar-reductive factors derived from functional cells into implant constructs, therefore, provide guidance in the design of more integrative biomaterial-based implantable devices for CNS repair.

Detection of radiation-induced brain necrosis in live rats using label-free time-resolved fluorescence spectroscopy (TRFS) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hartl, Brad A.; Ma, Htet S. W.; Sridharan, Shamira; Hansen, Katherine; Klich, Melanie; Perks, Julian; Kent, Michael; Kim, Kyoungmi; Fragoso, Ruben; Marcu, Laura

2017-02-01

Differentiating radiation-induced necrosis from recurrent tumor in the brain remains a significant challenge to the neurosurgeon. Clinical imaging modalities are not able to reliably discriminate the two tissue types, making biopsy location selection and surgical management difficult. Label-free fluorescence lifetime techniques have previously been shown to be able to delineate human brain tumor from healthy tissues. Thus, fluorescence lifetime techniques represent a potential means to discriminate the two tissues in real-time during surgery. This study aims to characterize the endogenous fluorescence lifetime signatures from radiation induced brain necrosis in a tumor-free rat model. Fischer rats received a single fraction of 60 Gy of radiation to the right hemisphere using a linear accelerator. Animals underwent a terminal live surgery after gross necrosis had developed, as verified with MRI. During surgery, healthy and necrotic brain tissue was measured with a fiber optic needle connected to a multispectral fluorescence lifetime system. Measurements of the necrotic tissue showed a 48% decrease in intensity and 20% increase in lifetimes relative to healthy tissue. Using a support vector machine classifier and leave-one-out validation technique, the necrotic tissue was correctly classified with 94% sensitivity and 97% specificity. Spectral contribution analysis also confirmed that the primary source of fluorescence contrast lies within the redox and bound-unbound population shifts of nicotinamide adenine dinucleotide. A clinical trial is presently underway to measure these tissue types in humans. These results show for the first time that radiation-induced necrotic tissue in the brain contains significantly different metabolic signatures that are detectable with label-free fluorescence lifetime techniques.

Light interference as a possible stressor altering HSP70 and its gene expression levels in brain and hepatic tissues of golden spiny mice.

PubMed

Ashkenazi, Lilach; Haim, Abraham

2012-11-15

Light at night and light interference (LI) disrupt the natural light:dark cycle, causing alterations at physiological and molecular levels, partly by suppressing melatonin (MLT) secretion at night. Heat shock proteins (HSPs) can be activated in response to environmental changes. We assessed changes in gene expression and protein level of HSP70 in brain and hepatic tissues of golden spiny mice (Acomys russatus) acclimated to LI for two (SLI), seven (MLI) and 21 nights (LLI). The effect of MLT treatment on LI-mice was also assessed. HSP70 levels increased in brain and hepatic tissues after SLI, whereas after MLI and LLI, HSP70 decreased to control levels. Changes in HSP70 levels as a response to MLT occurred after SLI only in hepatic tissue. However, hsp70 expression following SLI increased in brain tissue, but not in hepatic tissue. MLT treatment and SLI caused a decrease in hsp70 levels in brain tissue and an increase in hsp70 in hepatic tissue. SLI acclimation elicited a stress response in A. russatus, as expressed by increased HSP70 levels and gene expression. Longer acclimation decreases protein and gene expression to their control levels. We conclude that for brain and hepatic tissues of A. russatus, LI is a short-term stressor. Our results also revealed that A. russatus can acclimate to LI, possibly because of its circadian system plasticity, which allows it to behave both as a nocturnal and as a diurnal rodent. To the best of our knowledge, this is the first study showing the effect of LI as a stressor at the cellular level, by activating HSP70.

Distribution of lead in the brain tissues from DNTC patients using synchrotron radiation microbeams

NASA Astrophysics Data System (ADS)

Ide-Ektessabi, Ari; Ota, Yukihide; Ishihara, Ryoko; Mizuno, Yutaka; Takeuchi, Tohru

2005-12-01

Diffuse neurofibrillary tangles with calcification (DNTC) is a form of dementia with certain characteristics. Its pathology is characterized by cerebrum atrophy, calcification on globus pallidus and dentate nucleus and diffuse neurofibrillary tangles without senile plaques. In the present study brain tissues were prepared from patients with patients DNTC, calcified and non-calcified Alzheimer's disease (AD) patients. The brain tissues were examined non-destructively by X-ray fluorescence (XRF) spectroscopy using synchrotron radiation (SR) microbeams for trace metallic elements Ca, Fe, Cu, Zn and Pb. The XRF analysis showed that there were Pb concentrations in the calcified areas in the brain tissues with both DNTC and AD but there was none in those with non-calcified AD.

Brain Sex Matters: estrogen in cognition and Alzheimer’s disease

PubMed Central

Li, Rena; Cui, Jie; Shen, Yong

2014-01-01

Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissues such as liver, heart, muscle, bone and the brain. During the past decade, increasing evidence suggests that brain estrogen can not only be synthesized by neurons, but also by astrocytes. Brain estrogen also works locally at the site of synthesis in paracrine and/or intracrine fashion to maintain important tissue-specific functions. Here, we will focus on the biology of brain estrogen and its impact on cognitive function and Alzheimer’s disease. This comprehensive review provides new insights into brain estrogens by presenting a better understanding of the tissue-specific estrogen effects and their roles in healthy ageing and cognitive function. PMID:24418360

Expression of hypoxia-inducible carbonic anhydrases in brain tumors

PubMed Central

Proescholdt, Martin A.; Mayer, Christina; Kubitza, Marion; Schubert, Thomas; Liao, Shu-Yuan; Stanbridge, Eric J.; Ivanov, Sergey; Oldfield, Edward H.; Brawanski, Alexander; Merrill, Marsha J.

2005-01-01

Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel–Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-1α staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target. PMID:16212811

Dye-enhanced multimodal confocal imaging as a novel approach to intraoperative diagnosis of brain tumors.

PubMed

Snuderl, Matija; Wirth, Dennis; Sheth, Sameer A; Bourne, Sarah K; Kwon, Churl-Su; Ancukiewicz, Marek; Curry, William T; Frosch, Matthew P; Yaroslavsky, Anna N

2013-01-01

Intraoperative diagnosis plays an important role in accurate sampling of brain tumors, limiting the number of biopsies required and improving the distinction between brain and tumor. The goal of this study was to evaluate dye-enhanced multimodal confocal imaging for discriminating gliomas from nonglial brain tumors and from normal brain tissue for diagnostic use. We investigated a total of 37 samples including glioma (13), meningioma (7), metastatic tumors (9) and normal brain removed for nontumoral indications (8). Tissue was stained in 0.05 mg/mL aqueous solution of methylene blue (MB) for 2-5 minutes and multimodal confocal images were acquired using a custom-built microscope. After imaging, tissue was formalin fixed and paraffin embedded for standard neuropathologic evaluation. Thirteen pathologists provided diagnoses based on the multimodal confocal images. The investigated tumor types exhibited distinctive and complimentary characteristics in both the reflectance and fluorescence responses. Images showed distinct morphological features similar to standard histology. Pathologists were able to distinguish gliomas from normal brain tissue and nonglial brain tumors, and to render diagnoses from the images in a manner comparable to haematoxylin and eosin (H&E) slides. These results confirm the feasibility of multimodal confocal imaging for intravital intraoperative diagnosis. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

NASA Robotic Neurosurgery Testbed

NASA Technical Reports Server (NTRS)

Mah, Robert

1997-01-01

The detection of tissue interface (e.g., normal tissue, cancer, tumor) has been limited clinically to tactile feedback, temperature monitoring, and the use of a miniature ultrasound probe for tissue differentiation during surgical operations, In neurosurgery, the needle used in the standard stereotactic CT or MRI guided brain biopsy provides no information about the tissue being sampled. The tissue sampled depends entirely upon the accuracy with which the localization provided by the preoperative CT or MRI scan is translated to the intracranial biopsy site. In addition, no information about the tissue being traversed by the needle (e.g., a blood vessel) is provided. Hemorrhage due to the biopsy needle tearing a blood vessel within the brain is the most devastating complication of stereotactic CT/MRI guided brain biopsy. A robotic neurosurgery testbed has been developed at NASA Ames Research Center as a spin-off of technologies from space, aeronautics and medical programs. The invention entitled "Robotic Neurosurgery Leading to Multimodality Devices for Tissue Identification" is nearing a state ready for commercialization. The devices will: 1) improve diagnostic accuracy and precision of general surgery, with near term emphasis on stereotactic brain biopsy, 2) automate tissue identification, with near term emphasis on stereotactic brain biopsy, to permit remote control of the procedure, and 3) reduce morbidity for stereotactic brain biopsy. The commercial impact from this work is the potential development of a whole new generation of smart surgical tools to increase the safety, accuracy and efficiency of surgical procedures. Other potential markets include smart surgical tools for tumor ablation in neurosurgery, general exploratory surgery, prostate cancer surgery, and breast cancer surgery.

NASA Robotic Neurosurgery Testbed

NASA Technical Reports Server (NTRS)

Mah, Robert

1997-01-01

The detection of tissue interface (e.g., normal tissue, cancer, tumor) has been limited clinically to tactile feedback, temperature monitoring, and the use of a miniature ultrasound probe for tissue differentiation during surgical operations. In neurosurgery, the needle used in the standard stereotactic CT (Computational Tomography) or MRI (Magnetic Resonance Imaging) guided brain biopsy provides no information about the tissue being sampled. The tissue sampled depends entirely upon the accuracy with which the localization provided by the preoperative CT or MRI scan is translated to the intracranial biopsy site. In addition, no information about the tissue being traversed by the needle (e.g., a blood vessel) is provided. Hemorrhage due to the biopsy needle tearing a blood vessel within the brain is the most devastating complication of stereotactic CT/MRI guided brain biopsy. A robotic neurosurgery testbed has been developed at NASA Ames Research Center as a spin-off of technologies from space, aeronautics and medical programs. The invention entitled 'Robotic Neurosurgery Leading to Multimodality Devices for Tissue Identification' is nearing a state ready for commercialization. The devices will: 1) improve diagnostic accuracy and precision of general surgery, with near term emphasis on stereotactic brain biopsy, 2) automate tissue identification, with near term emphasis on stereotactic brain biopsy, to permit remote control of the procedure, and 3) reduce morbidity for stereotactic brain biopsy. The commercial impact from this work is the potential development of a whole new generation of smart surgical tools to increase the safety, accuracy and efficiency of surgical procedures. Other potential markets include smart surgical tools for tumor ablation in neurosurgery, general exploratory surgery, prostate cancer surgery, and breast cancer surgery.

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

PubMed Central

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain. PMID:27057543

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder.

PubMed

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

[Effects of Geometrical Dimensions and Material Properties on the Rotation Characteristics of Head].

PubMed

Chen, Yue; Cui, Shihai; Li, Haiyan; Ruan, Shijie

2016-08-01

The validated finite element head model(FEHM)of a 3-year-old child,a 6-year-old child and a 50 th percentile adult were used to investigate the effects of head dimension and material parameters of brain tissues on the head rotational responses based on experimental design.Results showed that the effects of head dimension and directions of rotation on the head rotational responses were not significant under the same rotational loading condition,and the same results appeared in the viscoelastic material parameters of brain tissues.However,the head rotational responses were most sensitive to the shear modulus(G)of brain tissues relative to decay constant(β)and bulk modulus(K).Therefore,the selection of material parameters of brain tissues is most important to the accuracy of simulation results,especially in the study of brain injury criterion under the rotational loading conditions.

Focused fluorescence excitation with time-reversed ultrasonically encoded light and imaging in thick scattering media

NASA Astrophysics Data System (ADS)

Lai, Puxiang; Suzuki, Yuta; Xu, Xiao; Wang, Lihong V.

2013-07-01

Scattering dominates light propagation in biological tissue, and therefore restricts both resolution and penetration depth in optical imaging within thick tissue. As photons travel into the diffusive regime, typically 1 mm beneath human skin, their trajectories transition from ballistic to diffusive due to the increased number of scattering events, which makes it impossible to focus, much less track, photon paths. Consequently, imaging methods that rely on controlled light illumination are ineffective in deep tissue. This problem has recently been addressed by a novel method capable of dynamically focusing light in thick scattering media via time reversal of ultrasonically encoded (TRUE) diffused light. Here, using photorefractive materials as phase conjugate mirrors, we show a direct visualization and dynamic control of optical focusing with this light delivery method, and demonstrate its application for focused fluorescence excitation and imaging in thick turbid media. These abilities are increasingly critical for understanding the dynamic interactions of light with biological matter and processes at different system levels, as well as their applications for biomedical diagnosis and therapy.

Quantitative analysis of diffusion tensor orientation: theoretical framework.

PubMed

Wu, Yu-Chien; Field, Aaron S; Chung, Moo K; Badie, Benham; Alexander, Andrew L

2004-11-01

Diffusion-tensor MRI (DT-MRI) yields information about the magnitude, anisotropy, and orientation of water diffusion of brain tissues. Although white matter tractography and eigenvector color maps provide visually appealing displays of white matter tract organization, they do not easily lend themselves to quantitative and statistical analysis. In this study, a set of visual and quantitative tools for the investigation of tensor orientations in the human brain was developed. Visual tools included rose diagrams, which are spherical coordinate histograms of the major eigenvector directions, and 3D scatterplots of the major eigenvector angles. A scatter matrix of major eigenvector directions was used to describe the distribution of major eigenvectors in a defined anatomic region. A measure of eigenvector dispersion was developed to describe the degree of eigenvector coherence in the selected region. These tools were used to evaluate directional organization and the interhemispheric symmetry of DT-MRI data in five healthy human brains and two patients with infiltrative diseases of the white matter tracts. In normal anatomical white matter tracts, a high degree of directional coherence and interhemispheric symmetry was observed. The infiltrative diseases appeared to alter the eigenvector properties of affected white matter tracts, showing decreased eigenvector coherence and interhemispheric symmetry. This novel approach distills the rich, 3D information available from the diffusion tensor into a form that lends itself to quantitative analysis and statistical hypothesis testing. (c) 2004 Wiley-Liss, Inc.

The biochemical, nanomechanical and chemometric signatures of brain cancer

NASA Astrophysics Data System (ADS)

Abramczyk, Halina; Imiela, Anna

2018-01-01

Raman spectroscopy and imaging combined with AFM topography and mechanical indentation by AFM have been shown to be an effective tool for analysis and discrimination of human brain tumors from normal structures. Raman methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n = 5) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma (IV grade), and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational spectra and Raman images we provide a real-time feedback that is label-free method to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, and proteins. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm- 1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the lipid and protein contents of tumorous brain tissue compared to the non-tumor tissue. Almost all brain tumors have the Raman intensity ratios significantly higher (1.99 ± 0.026) than that found in non-tumor brain tissue, which is 1.456 ± 0.02, and indicates that the relative amount of lipids compared to proteins is significantly higher in the normal brain tissue. Mechanical indentation using AFM on sliced human brain tissues (medulloblastoma, grade IV) revealed that the mechanical properties of this tissue are strongly heterogeneous, between 1.8 and 75.7 kPa, and the mean of 27.16 kPa. The sensitivity and specificity obtained directly from PLSDA and cross validation gives a sensitivity and specificity of 98.5% and 96% and 96.3% and 92% for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development.

Age dependence of dielectric properties of bovine brain and ocular tissues in the frequency range of 400 MHz to 18 GHz

NASA Astrophysics Data System (ADS)

Schmid, Gernot; Überbacher, Richard

2005-10-01

In order to identify possible age-dependent dielectric properties of brain and eye tissues in the frequency range of 400 MHz to 18 GHz, measurements on bovine grey and white matter as well as on cornea, lens (cortical) and the vitreous body were performed using a commercially available open-ended coaxial probe and a computer-controlled vector network analyser. Freshly excised tissues of 52 animals of two age groups (42 adult animals, i.e. 16-24 month old and 10 young animals, i.e. 4-6 month old calves) were examined within 8 min (brain tissue) and 15 min (eye tissue), respectively, of the animals' death. Tissue temperatures for the measurements were 32 ± 1 °C and 25 ± 1 °C for brain and eye tissues, respectively. Statistical analysis of the measured data revealed significant differences in the dielectric properties of white matter and cortical lens tissue between the adult and the young group. In the case of white matter the mean values of conductivity and permittivity of young tissue were 15%-22% and 12%-15%, respectively, higher compared to the adult tissue in the considered frequency range. Similarly, young cortical lens tissue was 25%-76% higher in conductivity and 27%-39% higher in permittivity than adult cortical lens tissue.

Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

PubMed Central

Rabeneck, Demi B.; Martines, Roosecelis B.; Reagan-Steiner, Sarah; Ermias, Yokabed; Estetter, Lindsey B.C.; Suzuki, Tadaki; Ritter, Jana; Keating, M. Kelly; Hale, Gillian; Gary, Joy; Muehlenbachs, Atis; Lambert, Amy; Lanciotti, Robert; Oduyebo, Titilope; Meaney-Delman, Dana; Bolaños, Fernando; Saad, Edgar Alberto Parra; Shieh, Wun-Ju; Zaki, Sherif R.

2017-01-01

Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections. PMID:27959260

Coherent beam control through inhomogeneous media in multi-photon microscopy

NASA Astrophysics Data System (ADS)

Paudel, Hari Prasad

Multi-photon fluorescence microscopy has become a primary tool for high-resolution deep tissue imaging because of its sensitivity to ballistic excitation photons in comparison to scattered excitation photons. The imaging depth of multi-photon microscopes in tissue imaging is limited primarily by background fluorescence that is generated by scattered light due to the random fluctuations in refractive index inside the media, and by reduced intensity in the ballistic focal volume due to aberrations within the tissue and at its interface. We built two multi-photon adaptive optics (AO) correction systems, one for combating scattering and aberration problems, and another for compensating interface aberrations. For scattering correction a MEMS segmented deformable mirror (SDM) was inserted at a plane conjugate to the objective back-pupil plane. The SDM can pre-compensate for light scattering by coherent combination of the scattered light to make an apparent focus even at a depths where negligible ballistic light remains (i.e. ballistic limit). This problem was approached by investigating the spatial and temporal focusing characteristics of a broad-band light source through strongly scattering media. A new model was developed for coherent focus enhancement through or inside the strongly media based on the initial speckle contrast. A layer of fluorescent beads under a mouse skull was imaged using an iterative coherent beam control method in the prototype two-photon microscope to demonstrate the technique. We also adapted an AO correction system to an existing in three-photon microscope in a collaborator lab at Cornell University. In the second AO correction approach a continuous deformable mirror (CDM) is placed at a plane conjugate to the plane of an interface aberration. We demonstrated that this "Conjugate AO" technique yields a large field-of-view (FOV) advantage in comparison to Pupil AO. Further, we showed that the extended FOV in conjugate AO is maintained over a relatively large axial misalignment of the conjugate planes of the CDM and the aberrating interface. This dissertation advances the field of microscopy by providing new models and techniques for imaging deeply within strongly scattering tissue, and by describing new adaptive optics approaches to extending imaging FOV due to sample aberrations.

Analysis of human tissue optical scattering spectra for the purpose of breast cancer diagnostics using multi-layer perceptron

NASA Astrophysics Data System (ADS)

Nuzhny, Anton S.; Shumsky, Sergey A.; Korzhov, Alexey G.; Lyubynskaya, Tatiana E.

2008-02-01

Optical scattering spectra obtained in the clinical trials of breast cancer diagnostic system were analyzed for the purpose to detect in the dataflow the segments corresponding to malignant tissues. Minimal invasive probe with optical fibers inside delivers white light from the source and collects the scattering light while being moved through the tissue. The sampling rate is 100 Hz and each record contains the results of measurements of scattered light intensity at 184 fixed wavelength points. Large amount of information acquired in each procedure, fuzziness in criteria of 'cancer' family membership and data noisiness make neural networks to be an attractive tool for analysis of these data. To define the dividing rule between 'cancer' and 'non-cancer' spectral families a three-layer perceptron was applied. In the process of perceptron learning back propagation method was used to minimize the learning error. Regularization was done using the Bayesian approach. The learning sample was formed by the experts. End-to-end probability calculation throughout the procedure dataset showed reliable detection of the 'cancer' segments. Much attention was paid on the spectra of the tissues with high blood content. Often the reason is vessel injury caused by the penetrating optical probe. But also it can be a dense vessel net surrounding the malignant tumor. To make the division into 'cancer' and 'non-cancer' families for the tissues with high blood content a special perceptron was learnt exceptionally on such spectra.

Gene expression changes with age in skin, adipose tissue, blood and brain.

PubMed

Glass, Daniel; Viñuela, Ana; Davies, Matthew N; Ramasamy, Adaikalavan; Parts, Leopold; Knowles, David; Brown, Andrew A; Hedman, Asa K; Small, Kerrin S; Buil, Alfonso; Grundberg, Elin; Nica, Alexandra C; Di Meglio, Paola; Nestle, Frank O; Ryten, Mina; Durbin, Richard; McCarthy, Mark I; Deloukas, Panagiotis; Dermitzakis, Emmanouil T; Weale, Michael E; Bataille, Veronique; Spector, Tim D

2013-07-26

Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age. Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues. Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.

Tissue-like Neural Probes for Understanding and Modulating the Brain.

PubMed

Hong, Guosong; Viveros, Robert D; Zwang, Theodore J; Yang, Xiao; Lieber, Charles M

2018-03-19

Electrophysiology tools have contributed substantially to understanding brain function, yet the capabilities of conventional electrophysiology probes have remained limited in key ways because of large structural and mechanical mismatches with respect to neural tissue. In this Perspective, we discuss how the general goal of probe design in biochemistry, that the probe or label have a minimal impact on the properties and function of the system being studied, can be realized by minimizing structural, mechanical, and topological differences between neural probes and brain tissue, thus leading to a new paradigm of tissue-like mesh electronics. The unique properties and capabilities of the tissue-like mesh electronics as well as future opportunities are summarized. First, we discuss the design of an ultraflexible and open mesh structure of electronics that is tissue-like and can be delivered in the brain via minimally invasive syringe injection like molecular and macromolecular pharmaceuticals. Second, we describe the unprecedented tissue healing without chronic immune response that leads to seamless three-dimensional integration with a natural distribution of neurons and other key cells through these tissue-like probes. These unique characteristics lead to unmatched stable long-term, multiplexed mapping and modulation of neural circuits at the single-neuron level on a year time scale. Last, we offer insights on several exciting future directions for the tissue-like electronics paradigm that capitalize on their unique properties to explore biochemical interactions and signaling in a "natural" brain environment.

In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

PubMed

Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

2016-05-01

High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

Assessment of collagen changes in ovarian tissue by extracting optical scattering coefficient from OCT images

NASA Astrophysics Data System (ADS)

Yang, Yi; Wang, Tianheng; Biswal, Nrusingh; Wang, Xiaohong; Sanders, Melinda; Brewer, Molly; Zhu, Quing

2012-01-01

Optical scattering coefficient from ex-vivo unfixed normal and malignant ovarian tissue was quantitatively extracted by fitting optical coherence tomography (OCT) A-line signals to a single scattering model. 1097 average A-line measurements at a wavelength of 1310nm were performed at 108 sites obtained from 18 ovaries. The average scattering coefficient obtained from normal group consisted of 833 measurements from 88 sites was 2.41 mm-1 (+/-0.59), while the average coefficient obtained from malignant group consisted of 264 measurements from 20 sites was 1.55 mm-1 (+/-0.46). Using a threshold of 2 mm-1 for each ovary, a sensitivity of 100% and a specificity of 100% were achieved. The amount of collagen within OCT imaging depth was analyzed from the tissue histological section stained with Sirius Red. The average collagen area fraction (CAF) obtained from normal group was 48.4% (+/-12.3%), while the average CAF obtained from malignant group was 11.4% (+/-4.7%). Statistical significance of the collagen content was found between the two groups (p < 0.001). The preliminary data demonstrated that quantitative extraction of optical scattering coefficient from OCT images could be a potential powerful method for ovarian cancer detection and diagnosis.

Scatter Correction with Combined Single-Scatter Simulation and Monte Carlo Simulation Scaling Improved the Visual Artifacts and Quantification in 3-Dimensional Brain PET/CT Imaging with 15O-Gas Inhalation.

PubMed

Magota, Keiichi; Shiga, Tohru; Asano, Yukari; Shinyama, Daiki; Ye, Jinghan; Perkins, Amy E; Maniawski, Piotr J; Toyonaga, Takuya; Kobayashi, Kentaro; Hirata, Kenji; Katoh, Chietsugu; Hattori, Naoya; Tamaki, Nagara

2017-12-01

In 3-dimensional PET/CT imaging of the brain with 15 O-gas inhalation, high radioactivity in the face mask creates cold artifacts and affects the quantitative accuracy when scatter is corrected by conventional methods (e.g., single-scatter simulation [SSS] with tail-fitting scaling [TFS-SSS]). Here we examined the validity of a newly developed scatter-correction method that combines SSS with a scaling factor calculated by Monte Carlo simulation (MCS-SSS). Methods: We performed phantom experiments and patient studies. In the phantom experiments, a plastic bottle simulating a face mask was attached to a cylindric phantom simulating the brain. The cylindric phantom was filled with 18 F-FDG solution (3.8-7.0 kBq/mL). The bottle was filled with nonradioactive air or various levels of 18 F-FDG (0-170 kBq/mL). Images were corrected either by TFS-SSS or MCS-SSS using the CT data of the bottle filled with nonradioactive air. We compared the image activity concentration in the cylindric phantom with the true activity concentration. We also performed 15 O-gas brain PET based on the steady-state method on patients with cerebrovascular disease to obtain quantitative images of cerebral blood flow and oxygen metabolism. Results: In the phantom experiments, a cold artifact was observed immediately next to the bottle on TFS-SSS images, where the image activity concentrations in the cylindric phantom were underestimated by 18%, 36%, and 70% at the bottle radioactivity levels of 2.4, 5.1, and 9.7 kBq/mL, respectively. At higher bottle radioactivity, the image activity concentrations in the cylindric phantom were greater than 98% underestimated. For the MCS-SSS, in contrast, the error was within 5% at each bottle radioactivity level, although the image generated slight high-activity artifacts around the bottle when the bottle contained significantly high radioactivity. In the patient imaging with 15 O 2 and C 15 O 2 inhalation, cold artifacts were observed on TFS-SSS images, whereas no artifacts were observed on any of the MCS-SSS images. Conclusion: MCS-SSS accurately corrected the scatters in 15 O-gas brain PET when the 3-dimensional acquisition mode was used, preventing the generation of cold artifacts, which were observed immediately next to a face mask on TFS-SSS images. The MCS-SSS method will contribute to accurate quantitative assessments. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Evidence for brain glucose dysregulation in Alzheimer's disease.

PubMed

An, Yang; Varma, Vijay R; Varma, Sudhir; Casanova, Ramon; Dammer, Eric; Pletnikova, Olga; Chia, Chee W; Egan, Josephine M; Ferrucci, Luigi; Troncoso, Juan; Levey, Allan I; Lah, James; Seyfried, Nicholas T; Legido-Quigley, Cristina; O'Brien, Richard; Thambisetty, Madhav

2018-03-01

It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. Copyright © 2017 the Alzheimer's Association. All rights reserved.

Laser Desorption/Ionization Mass Spectrometric Imaging of Endogenous Lipids from Rat Brain Tissue Implanted with Silver Nanoparticles

NASA Astrophysics Data System (ADS)

Muller, Ludovic; Baldwin, Kathrine; Barbacci, Damon C.; Jackson, Shelley N.; Roux, Aurélie; Balaban, Carey D.; Brinson, Bruce E.; McCully, Michael I.; Lewis, Ernest K.; Schultz, J. Albert; Woods, Amina S.

2017-08-01

Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate (AgNP) matrix generates reproducible imaging of lipids in rodent models of disease and injury. Gas-phase production and acceleration of size-selected 8 nm AgNP is followed by controlled ion beam rastering and soft landing implantation of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality images for most lipid classes in rat brain tissue (in positive mode: galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides, sulfatides, phosphatidylinositol, and sphingomyelins). Image reproducibility in serial sections of brain tissue is achieved within <10% tolerance by selecting argentated instead of alkali cationized ions. The imaging of brain tissues spotted with pure standards was used to demonstrate that Ag cationized ceramide and diacylglycerol ions are from intact, endogenous species. In contrast, almost all Ag cationized fatty acid ions are a result of fragmentations of numerous lipid types having the fatty acid as a subunit. Almost no argentated intact fatty acid ions come from the pure fatty acid standard on tissue.

The national DBS brain tissue network pilot study: need for more tissue and more standardization.

PubMed

Vedam-Mai, V; Krock, N; Ullman, M; Foote, K D; Shain, W; Smith, K; Yachnis, A T; Steindler, D; Reynolds, B; Merritt, S; Pagan, F; Marjama-Lyons, J; Hogarth, P; Resnick, A S; Zeilman, P; Okun, M S

2011-08-01

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

In vivo measurements of optical properties of human muscles with visible and near infrared reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Wang, Chiao Yi; Yu, Ting Wen; Sung, Kung Bin

2018-02-01

Estimating optical properties of tissues is a crucial step to model photon migration in tissue, facilitate the design of the probe geometry, better interpret data measured from tissue and predict photon energy distributions in tissue for various diagnostic and therapeutic applications. Diffuse reflectance spectroscopy (DRS) using visible and near-infrared light is a well-known method for estimating optical properties of tissues. For estimating optical properties of muscles, most existing researches have used integrating spheres for ex-vivo measurements. However, due to inter-subject variability and sitespecific conditions, an in-vivo approach can provide more accurate estimations of muscle absorption and scattering coefficients, which is important for the tomographic reconstruction of changes in the absorption or fluorescence in tissue. In this study, we used DRS with wavelengths between 600 nm and 800 nm and a fiber bundle with source-to-detector separations in the range of 0.18-0.35 cm to quantify wavelength-dependent scattering and absorption coefficients of human muscles in vivo with an inverse Monte Carlo model. Reflectance spectra were measured on the neck and the upper arm of one volunteer. After calibrating spectra with tissue phantoms made of Intralipid and India ink, we estimated scattering and absorption coefficients of muscles. The results are compared to those measured ex vivo in the literature.

Organization of brain tissue - Is the brain a noisy processor.

NASA Technical Reports Server (NTRS)

Adey, W. R.

1972-01-01

This paper presents some thoughts on functional organization in cerebral tissue. 'Spontaneous' wave and unit firing are considered as essential phenomena in the handling of information. Various models are discussed which have been suggested to describe the pseudorandom behavior of brain cells, leading to a view of the brain as an information processor and its role in learning, memory, remembering and forgetting.

Brain extraction from normal and pathological images: A joint PCA/Image-Reconstruction approach.

PubMed

Han, Xu; Kwitt, Roland; Aylward, Stephen; Bakas, Spyridon; Menze, Bjoern; Asturias, Alexander; Vespa, Paul; Van Horn, John; Niethammer, Marc

2018-08-01

Brain extraction from 3D medical images is a common pre-processing step. A variety of approaches exist, but they are frequently only designed to perform brain extraction from images without strong pathologies. Extracting the brain from images exhibiting strong pathologies, for example, the presence of a brain tumor or of a traumatic brain injury (TBI), is challenging. In such cases, tissue appearance may substantially deviate from normal tissue appearance and hence violates algorithmic assumptions for standard approaches to brain extraction; consequently, the brain may not be correctly extracted. This paper proposes a brain extraction approach which can explicitly account for pathologies by jointly modeling normal tissue appearance and pathologies. Specifically, our model uses a three-part image decomposition: (1) normal tissue appearance is captured by principal component analysis (PCA), (2) pathologies are captured via a total variation term, and (3) the skull and surrounding tissue is captured by a sparsity term. Due to its convexity, the resulting decomposition model allows for efficient optimization. Decomposition and image registration steps are alternated to allow statistical modeling of normal tissue appearance in a fixed atlas coordinate system. As a beneficial side effect, the decomposition model allows for the identification of potentially pathological areas and the reconstruction of a quasi-normal image in atlas space. We demonstrate the effectiveness of our approach on four datasets: the publicly available IBSR and LPBA40 datasets which show normal image appearance, the BRATS dataset containing images with brain tumors, and a dataset containing clinical TBI images. We compare the performance with other popular brain extraction models: ROBEX, BEaST, MASS, BET, BSE and a recently proposed deep learning approach. Our model performs better than these competing approaches on all four datasets. Specifically, our model achieves the best median (97.11) and mean (96.88) Dice scores over all datasets. The two best performing competitors, ROBEX and MASS, achieve scores of 96.23/95.62 and 96.67/94.25 respectively. Hence, our approach is an effective method for high quality brain extraction for a wide variety of images. Copyright © 2018 Elsevier Inc. All rights reserved.