DETECTION OF HUMAN BRAIN CANCER USING VISUALIZATION TECHNIQUE

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1 Proceeding of NCRIET-2015 & Indian J.Sci.Res. 12(1): , 2015 ISSN: (Print) ISSN: (Online) DETECTION OF HUMAN BRAIN CANCER USING VISUALIZATION TECHNIQUE OF OPTICAL COHERENCE TOMOGRAPHY SRUTHI SARATH a1, SACHIN KUMAR b, M. SHRISHANTI c AND VIDYASHREE d acd Student ECE, NIT, Raichur, India b Assistant Professor, NIT, Raichur, India ABSTRACT In this paper, discussed about detection of human brain cancer using optical coherence tomography (OCT) is an emerging biomedical imaging technology that has been applied to a wide range of biological, medical & material investigations. Intraoperative detection of residual tumor remains an important challenge in surgery to treat gliomas. New developments in optical techniques offer non-invasive high-resolution imaging that may integrate well into the workflow of neurosurgical operations. Using an intracranial glioma model, we have recently shown that time domain optical coherence tomography (OCT) allows discrimination of normal brain, diffusely invaded brain tissue, and solid tumor. OCT imaging allowed acquisition of 2D and 3D data arrays for multiplanar analysis of the tumor to brain interface. In this study we have analyzed biopsy specimens of human brain tumors and we present the first feasibility study of Intraoperative OCT and post-image acquisition processing for non-invasive imaging of the brain and brain tumor. Optical coherence tomography non-contact measurements of brain and brain tumor tissue produced B-scan images of 4 mm in width and mm in depth at an axial and lateral optical resolution of 15 µm. OCT imaging demonstrated a different microstructure and characteristic signal attenuation profiles of tumor versus normal brain. Post-image acquisition processing and automated detection of the tissue to air interface was used to realign A-scans to compensate for image distortions caused by pulse- and respiration-induced movements of the target volume. This feasibility study has demonstrated that OCT analysis of the tissue microstructure and light attenuation characteristics discriminate normal brain, areas of tumor infiltrated brain, solid tumor, and necrosis. KEYWORDS: Brain Cancer, OCT Optical coherence tomography (OCT) is an emerging optical imaging modality in biomedical optics and medicine. OCT performs high resolution, cross-sectional imaging of the internal microstructure in biological tissues by measuring echoes of backscattered light. Tissue pathology can be imaged in situ and in real time with resolutions of 1 15 µm, one to two orders of magnitude finer than conventional ultrasound. The unique features of OCT make it a powerful imaging modality, which promises to enable many fundamental research and clinical applications. OCT performs cross-sectional imaging by measuring the magnitude and echo time delay of backscattered light. Cross-sectional images are generated by performing multiple axial measurements of echo time delay (axial scans or A- scans) and scanning the incident optical beam transversely. This produces a two-dimensional data set, which represents the optical backscattering in a cross-sectional plane through the tissue. Images, or B-scans, can be displayed in false color or grey scale to visualize tissue pathology. Three-dimensional, volumetric data sets can be generated by acquiring sequential cross-sectional images by scanning the incident optical beam in a raster pattern. Threedimensional OCT (3D-OCT) data contain comprehensive volumetric structural information and can be manipulated similar to MR or CT images. CANCER DETECTION BY OCT Optical Coherence Tomography, or OCT, is a technique for obtaining sub-surface images of translucent or opaque materials at a resolution equivalent to a low-power microscope. It is effectively optical ultrasound, imaging reflections from within tissue to provide cross-sectional images. OCT is attracting interest among the medical community because it provides tissue morphology imagery at much higher resolution (better than 10 µm) than other imaging modalities such as MRI or ultrasound. The key benefits of OCT are Live sub-surface images at near-microscopic resolution 1 Corresponding author

2 Instant, direct imaging of tissue morphology No preparation of the sample or subject No ionizing radiation OCT delivers high resolution because it is based on light, rather than sound or radio frequency. An optical beam is directed at the tissue, and a small portion of this light that reflects from sub-surface features is collected. Note that most light is not reflected but, rather, scatters off at large angles. In conventional imaging, this diffusely scattered light contributes background that obscures an image. However, in OCT, a technique called interferometry is used to record the optical path length of received photons allowing rejection of most photons that scatter multiple times before detection. Thus OCT can build up clear 3D images of thick samples by rejecting background signal while collecting light directly reflected from surfaces of interest. Within the range of noninvasive three-dimensional imaging techniques that have been introduced to the medical research community, OCT as an echo technique is similar to ultrasound imaging. Other medical imaging techniques such as computerized axial emission tomography do not use the echo-location principle tomography, magnetic resonance imaging, or positron. The technique is limited to imaging 1 to 2 mm below the surface in biological tissue, because at greater depths the proportion of light that escapes preparation of a biological specimen is required, and without scattering is too small to be detected. No special images can be obtained non-contact or through a transparent window or membrane. It is also important to note that the laser output from the instruments is low eye-safe near-infra-red light is used and no damage to the sample is therefore likely. The principle of OCT is white light or low coherence interferometry. The optical setup typically consists of an interferometer with a low coherence, broad bandwidth light source. Light is split into and recombined from reference and sample arm, respectively. Figure: Typical optical setup of single point OCT. Scanning the light beam on the sample enables non-invasive cross-sectional imaging up to 3 mm in depth with micrometer resolution. Time domain OCT In time domain OCT the pathlength of the reference arm is translated longitudinally in time. A property of low coherence interferometry is that interference, i.e. the series of dark and bright fringes, is only achieved when the path difference lies within the coherence length of the light source. This interference is called auto correlation in a symmetric interferometer (both arms have the same reflectivity), or cross-correlation in the common case. The envelope of this modulation changes as pathlength difference is varied, where the peak of the envelope corresponds to pathlength matching. The interference of two partially coherent light beams can be expressed in terms of the source intensity, Is, as I=K1Is+K2Is+2 (K1Is)(K2Is).Re[γ(T)] Single scattering and optical tomography Unscattered photons like x-rays andγ-rays have been used to obtain tomographic straight rayprojections for a long time. The mathematical problem of reconstructing a function from its straight ray projections has already been presented by Radon (1917). Its solution, the Fourier slice theorem, shows that some of the three-dimensional Fourier data of the object can be obtained from two-dimensional FTs of its projections. Because of its analogy to the Fourier diffraction theorem (Wolf 1969), we shall have a

3 closer look at this theorem: from the FT of an object function F(x, y, z) (Which, e.g. in x-ray computer tomography (CT) characterizes the two-dimensional distribution of the linear x-ray attenuation coefficient). ENHANCED OCT FOR BRAIN CANCER A major challenge in surgically removing tumors, particularly in the brain, is to cut out as much cancer as possible while leaving healthy tissue intact. Currently available imaging tools to aid doctors during brain surgery, such as low resolution ultrasound, and time-consuming and expensive MRI, do not provide continuous guidance. A Johns Hopkins research team, led by Xingde Li, PhD, professor of biomedical engineering, has been working to further expand optical coherence tomography (OCT) technology first developed in the early 1990s for imaging the retina to organs beyond the eye. OCT produces high resolution images using lightwaves without delivering ionizing radiation to patients. Team member, Carmen Kut, an MD/PhD student working in Li s lab, thought OCT might provide a solution to the problem of separating brain cancers from other tissue during surgery. The researchers figured out that brain cancer cells lack myelin sheaths that coat healthy brain cells. Using this brain cancer OCT signature, the team devised a computer algorithm to process OCT data and, nearly instantaneously, generate a color-coded tissue map displaying cancer in red and healthy tissue in green. We envision that the OCT would be aimed at the area being operated on, and the surgeon could look at a screen to get a continuously updated picture of where the cancer is and isn t, Li says. So far the team has tested the system on fresh human brain tissue removed during surgeries and in surgeries to remove brain tumors from mice, say Carmen Kut. The researchers hope to begin clinical trials in patients this summer.alfredo Quinones-Hinojosa, MD, a professor of neurosurgery, neuroscience and oncology at the Johns Hopkins University School of Medicine, and the clinical leader of the research team feels that if those trials are successful and the system goes to market, it will be a big step up from imaging technologies now available during surgeries. Quinones-Hinojosa stated, Ultrasound has a much lower resolution than OCT, and MRI scanners designed to be wheeled over a patient on the operating table cost several millions of dollars each and require an extra hour of operating room time to obtain a single image. By comparison, the team anticipates that the cost of an OCT-based system would run in the hundreds of thousands of dollars. And, this technology has the potential to be adapted to detect cancers in other parts of the body, Kut says. She is working on combining OCT with different imaging techniques/algorithms that would detect blood vessels to help surgeons avoid cutting them. MATERIALS AND METHODS Instrument The experimental arrangement of FF-OCT (Fig. 1A) is based on a configuration that is referred to as a Linnik interferometer (Dubois et al., 2002). A halogen lamp is used as a spatially incoherent source to illuminate the full field of an immersion microscope objective at a central wavelength of 700 nm, with spectral width of 125 nm. The signal is extracted from the background of incoherent backscattered light using a phase-shifting method implemented in custom-designed software. This study was performed on a commercial FF-OCT system (LightCT, LLTech, France). Figure: System schematic (A), photograph (B), sample holder close up (C), and sample close up (D) FF-OCT imaging identifies myelinated axon fibers, neuronal cell bodies and vasculature in the human epileptic brain and cerebellum The cortex and the white matter are clearly distinguished from one another. Indeed, a subpopulation of neuronal cell bodies as well as myelinated axon bundles leading to

4 the white matter could be recognized. Neuronal cell bodies appear as dark triangles in relation to the bright surrounding myelinated environment. The FF- OCT signal is produced by backscattered photons from tissues of differing refractive indices. The number of photons backscattered from the nuclei in neurons appears to be too few to produce a signal that allows their differentiation from the cytoplasm, and therefore the whole of the cell body (nucleus plus cytoplasm) appears dark. OCT B-scan images. For ex vivo OCT imaging the tissue was immediately placed on ice and the resection plain was imaged. Following analysis, the tissue was fixed in formalin 4.5% and was then paraffin embedded for standard histological processing. Histological sections were evaluated by the Department of Neuropathology. Specimens of human brain tumors were obtained at surgery under protocol # granted by the ethics committee of the University of Lübeck. Informed consent was given by patients 24 h prior to surgery. Tumor tissue was removed using standard microsurgical techniques and the resection site of individual tissue blocks was documented by marker acquisition using a vector vision2 neuronavigation system (BrainLab, Heimstetten, Germany), which allowed correlation of MRI signal characteristics and The resection of intrinsic brain tumors is challenged by the fact that these tumors do not have a defined edge delineating the tumor mass from the adjacent normal brain. Since the early days of the surgical treatment of gliomas, neurosurgeons have used the guidance of anatomical landmarks, the color and texture of tumor tissue, and the tendency to hemorrhage from resection plains. Although recognition of solid tumor or tumor necrosis based on these criteria is relatively safe, even with the aid of an operating microscope it has remained difficult to delineate highly cellular tumor or densely invaded brain from normal or lightly invaded brain. The highly cellular part of the tumor on MRI roughly corresponds to the area of gadolinium contrast enhancement. The extent of removal of this contrastenhancing tumor correlates with survival of the patient. However, the surgeon s estimate of complete removal of visible tumor may only correlate with clearance of enhancement on MRI in about 30% of cases, which reflects the difficulty of the intraoperative detection of residual tumor.

5 Therefore, techniques for the intraoperative detection of highly cellular areas at the edge of the resection cavity may improve the chances of the complete removal of a tumor and may influence overall survival of a patient treated with a malignant glioma. Optical coherence tomography images consist of parallel A-scans along a scan line forming a two-dimensional B-scan image. Analysis of individual A-scans provides depth information on the signal intensity. Time domain optical coherence tomography A Sirius 713 Tomograph (4Optics AG, Luebeck, Germany) developed at the Institute for Biomedical Optics, University of Lübeck, Germany was modified for intraoperative use. A superluminescence diode (SLD) served as a light source emitting light at a near infrared wavelength with a central wavelength of 1310 nm and a coherence length of 15 µm (Fig. 1). The light is launched into an optical mono mode fiber, which guides the radiation to a modified OCT adapter containing a lens system with a working distance of 10 cm and an integrated pilot laser. The angle at which the laser enters the tissue should remain between 30 and 150 for optimal image information. Reflection artifacts from fluids on the tissue surface may occur at an exact angle of 90 (Böhringer et al., manuscript in preparation). This allows measurements of brain tissue and brain tumor tissue in a no-touch technique and produces 2D B-scan-like images of 4 mm in width and mm in depth, depending on the tissue characteristics. The image acquisition time at a resolution of 100 pixels/mm was about 8 s for a 4-mm scan line. The configuration used in this study provided axial and lateral optical resolutions of 15 µm. RESULTS Optical coherence tomography non-contact measurements of brain and brain tumor tissue produced B-scan images of 4 mm in width and mm in depth at an axial and lateral optical resolution of 15 µm. OCT imaging demonstrated a different microstructure and characteristic signal attenuation profiles of tumor versus normal brain. Post-image acquisition processing and automated detection of the tissue to air interface was used to realign A-scans to compensate for image distortions caused by pulse- and respiration-induced movements of the target volume. Realigned images allowed monitoring of intensity changes within the scan line and facilitated selection of areas for the averaging of A-scans and the calculation of attenuation coefficients for specific regions of interest. CONCLUSIONS This feasibility study has demonstrated that OCT analysis of the tissue microstructure and light attenuation characteristics discriminate normal brain, areas of tumor infiltrated brain, solid tumor, and necrosis. The working distance of the OCT adapter and the A-scan acquisition rate conceptually allows integration of the OCT applicator into the optical path of the operating microscopes. This would allow a continuous analysis of the resection plain, providing optical tomography, thereby adding a third dimension to the microscopic view and information on the light attenuation characteristics of the tissue. REFERENCES Albert FK, Forsting M, Sartor K, Adams HP, Kunze S. Early postoperative magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual tumor and its influence on regrowth and prognosis. Neurosurgery. 1994;34: doi: /

6 Bizheva K, Unterhuber A, Hermann B, Povazay B, Sattmann H, Drexler W, et al. Imaging ex vivo and in vitro brain morphology in animal models with ultrahigh resolution optical coherence tomography. J Biomed Opt. 2004;9: doi: / Bizheva K, Unterhuber A, Hermann B, Povazay B, Sattmann H, Fercher AF, et al. Imaging ex vivo healthy and pathological human brain tissue with ultra-high-resolution optical coherence tomography. J Biomed Opt. 2005;10: doi: / Böhringer HJ, Boller D, Leppert J, Knopp U, Lankenau E, Reusche E, et al. Time domain and spectral domain optical coherence tomography in the analysis of brain tumor tissue. Lasers Surg Med. 2006;38: doi: /lsm Böhringer HJ, Lankenau E, Rohde V, Hüttmann G, Giese A. Optical coherence tomography for experimental neuroendoscopy. Minim Invasive Neurosurg. 2006;49: doi: /s Boppart SA. Optical coherence tomography: technology and applications for neuroimaging. Psychophysiology. 2003;40: doi: / Boppart SA, Brezinski ME, Pitris C, Fujimoto JG. Optical coherence tomography for neurosurgical imaging of human intracortical melanoma. Neurosurgery. 1998;43: doi: /