We recently developed a nonlinear optical imaging technique based on second harmonic generation (SHG) to identify membrane disruption events in live cells. This technique was used to detect nanoporation in the plasma membrane following nanosecond pulsed electric field (nsPEF) exposure. It has been hypothesized that similar poration events could be induced by the thermal gradients generated by infrared (IR) laser energy. Optical pulses are a highly desirable stimulus for the nervous system, as they are capable of inhibiting and producing action potentials in a highly localized but non-contact fashion. However, the underlying mechanisms involved with infrared neural stimulation (INS) are not well understood. The ability of our method to non-invasively measure membrane structure and transmembrane potential via Two Photon Fluorescence (TPF) make it uniquely suited to neurological research. In this work, we leverage our technique to understand what role membrane structure plays during INS and contrast it with nsPEF stimulation. We begin by examining the effect of IR pulses on CHO-K1 cells before progressing to primary hippocampal neurons. The use of these two cell lines allows us to directly compare poration as a result of IR pulses to nsPEF exposure in both a neuron-derived cell line, and one likely lacking native channels sensitive to thermal stimuli.
{"title":"The role of membrane dynamics in electrical and infrared neural stimulation","authors":"Erick Moen, H. Beier, B. Ibey, A. Armani","doi":"10.1117/12.2214474","DOIUrl":"https://doi.org/10.1117/12.2214474","url":null,"abstract":"We recently developed a nonlinear optical imaging technique based on second harmonic generation (SHG) to identify membrane disruption events in live cells. This technique was used to detect nanoporation in the plasma membrane following nanosecond pulsed electric field (nsPEF) exposure. It has been hypothesized that similar poration events could be induced by the thermal gradients generated by infrared (IR) laser energy. Optical pulses are a highly desirable stimulus for the nervous system, as they are capable of inhibiting and producing action potentials in a highly localized but non-contact fashion. However, the underlying mechanisms involved with infrared neural stimulation (INS) are not well understood. The ability of our method to non-invasively measure membrane structure and transmembrane potential via Two Photon Fluorescence (TPF) make it uniquely suited to neurological research. In this work, we leverage our technique to understand what role membrane structure plays during INS and contrast it with nsPEF stimulation. We begin by examining the effect of IR pulses on CHO-K1 cells before progressing to primary hippocampal neurons. The use of these two cell lines allows us to directly compare poration as a result of IR pulses to nsPEF exposure in both a neuron-derived cell line, and one likely lacking native channels sensitive to thermal stimuli.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115567267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Villiger, A. Karanasos, Jian Ren, N. Lippok, M. Shishkov, J. Daemen, N. Van Mieghem, R. Diletti, M. Valgimigli, R. V. van Geuns, P. D. de Jaegere, F. Zijlstra, G. van Soest, S. Nadkarni, E. Regar, B. Bouma
Polarization sensitive (PS) OCT measures the polarization states of the light backscattered by tissue and provides measures of tissue birefringence and depolarization in addition to the structural OCT signal. Ex vivo studies have demonstrated that birefringence is increased in tissue rich in collagen and with elevated smooth muscle cell content. Preliminary data further suggests that depolarization can identify regions of macrophage infiltration, lipid, and irregularly arranged collagen fibers. These are important aspects of the mechanical integrity and vulnerability of atherosclerotic plaques. To evaluate the potential of PS-OCT in the clinical setting, we combined our custom PS-OCT system with commercially available OCT catheters (Fastview, Terumo Corporation) and performed a pilot study in 30 patients, scheduled to undergo percutaneous coronary intervention (PCI) on the grounds of stable or unstable angina. A total of 82 pullbacks in 39 vessels were performed, either in the native coronary arteries or post procedure. Comparing consecutive pullbacks of the same coronary artery, we found excellent agreement between the polarization features in the repeat pullbacks, validating the repeatability and robustness of PS-OCT in the clinical in vivo setting. In addition we observed that the birefringence and depolarization features vary significantly across lesions with identical structural OCT appearance, suggesting morphological subtypes. This first human pilot study proved the feasibility and robustness of intravascular PS-OCT. PS-OCT achieves improved tissue characterization and may help in identifying high-risk plaques, with the potential to ultimately improve risk stratification and help guiding PCI.
{"title":"First clinical pilot study with intravascular polarization sensitive optical coherence tomography (Conference Presentation)","authors":"M. Villiger, A. Karanasos, Jian Ren, N. Lippok, M. Shishkov, J. Daemen, N. Van Mieghem, R. Diletti, M. Valgimigli, R. V. van Geuns, P. D. de Jaegere, F. Zijlstra, G. van Soest, S. Nadkarni, E. Regar, B. Bouma","doi":"10.1117/12.2211463","DOIUrl":"https://doi.org/10.1117/12.2211463","url":null,"abstract":"Polarization sensitive (PS) OCT measures the polarization states of the light backscattered by tissue and provides measures of tissue birefringence and depolarization in addition to the structural OCT signal. Ex vivo studies have demonstrated that birefringence is increased in tissue rich in collagen and with elevated smooth muscle cell content. Preliminary data further suggests that depolarization can identify regions of macrophage infiltration, lipid, and irregularly arranged collagen fibers. These are important aspects of the mechanical integrity and vulnerability of atherosclerotic plaques. To evaluate the potential of PS-OCT in the clinical setting, we combined our custom PS-OCT system with commercially available OCT catheters (Fastview, Terumo Corporation) and performed a pilot study in 30 patients, scheduled to undergo percutaneous coronary intervention (PCI) on the grounds of stable or unstable angina. A total of 82 pullbacks in 39 vessels were performed, either in the native coronary arteries or post procedure. Comparing consecutive pullbacks of the same coronary artery, we found excellent agreement between the polarization features in the repeat pullbacks, validating the repeatability and robustness of PS-OCT in the clinical in vivo setting. In addition we observed that the birefringence and depolarization features vary significantly across lesions with identical structural OCT appearance, suggesting morphological subtypes. This first human pilot study proved the feasibility and robustness of intravascular PS-OCT. PS-OCT achieves improved tissue characterization and may help in identifying high-risk plaques, with the potential to ultimately improve risk stratification and help guiding PCI.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"162 36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121890203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Imaging cellular heterogeneity in cancer (Conference Presentation)","authors":"M. Skala","doi":"10.1117/12.2235249","DOIUrl":"https://doi.org/10.1117/12.2235249","url":null,"abstract":"Abstract not available.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"16 1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116712080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Addressing biophotonics challenges: deep penetration with needles and alternate contrast with micro-elastography (Conference Presentation)","authors":"D. Sampson","doi":"10.1117/12.2235252","DOIUrl":"https://doi.org/10.1117/12.2235252","url":null,"abstract":"Abstract not available.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"05 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127138616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Childs, R. Hogg, K. Groom, D. Revin, I. Rehman, J. Cockburn, S. Matcher
FTIR spectroscopy using a thermal light source has been the dominant method for obtaining infrared spectra since the 1950’s. Unfortunately the limited surface brightness and low spatial coherence of black-body radiators limits the spectral SNR in microspectroscopy and stand-off detection. Two recent innovations are addressing this problem a) FTIR instruments illuminated by high-spatial coherence broad-band supercontinuum sources and b) high spatial coherence narrow-band EC-QCL’s. Here we ask whether these two approaches offer equivalent sensitivity. By noting an analogy with near-infrared optical coherence tomography we rigorously show that the high temporal coherence of the EC-QCL brings an additional, very large SNR advantage over an FTIR instrument illuminated by a supercontinuum source under otherwise matched conditions. Specifically if a spectrum containing N points is recorded by both instruments using the same illumination intensity and the same detector noise level, then the EC-QCL can deliver a given spectral SNR in a time xN shorter than the FTIR instrument. This factor can reach x100, potentially even x1000, in realistic applications. We exploit the analogy with OCT further by developing a mid-infrared “swept laser”, using commercially available components, in which the tuning rate is much higher than in commercial EC-QCL devices. We use this swept laser to demonstrate the SNR advantage experimentally, using a custom-made EC-QCL spectrometer and PDMS polymer samples. We explore the potential upper limits on spectral acquisition rates, both from the fundamental kinetics of gain build-up in the external cavity and from likely mechanical limits on cavity tuning rates.
{"title":"Rigorous comparison of the spectral SNR of FTIR and EC-QCL spectroscopy (Conference Presentation)","authors":"D. Childs, R. Hogg, K. Groom, D. Revin, I. Rehman, J. Cockburn, S. Matcher","doi":"10.1117/12.2209063","DOIUrl":"https://doi.org/10.1117/12.2209063","url":null,"abstract":"FTIR spectroscopy using a thermal light source has been the dominant method for obtaining infrared spectra since the 1950’s. Unfortunately the limited surface brightness and low spatial coherence of black-body radiators limits the spectral SNR in microspectroscopy and stand-off detection. Two recent innovations are addressing this problem a) FTIR instruments illuminated by high-spatial coherence broad-band supercontinuum sources and b) high spatial coherence narrow-band EC-QCL’s. Here we ask whether these two approaches offer equivalent sensitivity. By noting an analogy with near-infrared optical coherence tomography we rigorously show that the high temporal coherence of the EC-QCL brings an additional, very large SNR advantage over an FTIR instrument illuminated by a supercontinuum source under otherwise matched conditions. Specifically if a spectrum containing N points is recorded by both instruments using the same illumination intensity and the same detector noise level, then the EC-QCL can deliver a given spectral SNR in a time xN shorter than the FTIR instrument. This factor can reach x100, potentially even x1000, in realistic applications. We exploit the analogy with OCT further by developing a mid-infrared “swept laser”, using commercially available components, in which the tuning rate is much higher than in commercial EC-QCL devices. We use this swept laser to demonstrate the SNR advantage experimentally, using a custom-made EC-QCL spectrometer and PDMS polymer samples. We explore the potential upper limits on spectral acquisition rates, both from the fundamental kinetics of gain build-up in the external cavity and from likely mechanical limits on cavity tuning rates.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114218842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acute and long-term effects of neural implants examined with two-photon and optical coherence microscopy (Conference Presentation)","authors":"D. Hammer","doi":"10.1117/12.2225243","DOIUrl":"https://doi.org/10.1117/12.2225243","url":null,"abstract":"The abstract is not available","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127744678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This paper explores the utility of reflective THz imaging to assess the viability of surgical flaps. Flap surgery is a technique where tissue is harvested from a donor site and moved to a recipient while keeping the blood supply intact. This technique is common in head and neck tumor resection surgery where the reconstruction of complex and sensitive anatomic structures is routine following the resection of large and/or invasive tumors. Successful flap surgery results in tissue that is sufficiently perfused with both blood and extracellular water. If insufficient fluid levels are maintained, the flap tissue becomes necrotic and must be excised immediately to prevent infection developing and spreading to the surrounding areas. The goal of this work is to investigate the hydration of surgical flaps and correlate image features to successful graft outcomes. Advancement flaps were created on the abdomens of rat models. One rat model was labeled control and care was taken to ensure a successful flap outcome. The flap on the second rat was compromised with restricted blood flow and allowed to fail. The flaps of both rats were imaged once a day over the course of a week at which point the compromised flap had begun to show signs of necrosis. Significant differences in tissue water content were observed between rats over the experimental period. The results suggest that THz imaging may enable early assessment of flap viability.
{"title":"In situ monitoring of surgical flap viability using THz imaging (Conference Presentation)","authors":"N. Bajwa, S. Sung, W. Grundfest, Z. Taylor","doi":"10.1117/12.2218572","DOIUrl":"https://doi.org/10.1117/12.2218572","url":null,"abstract":"This paper explores the utility of reflective THz imaging to assess the viability of surgical flaps. Flap surgery is a technique where tissue is harvested from a donor site and moved to a recipient while keeping the blood supply intact. This technique is common in head and neck tumor resection surgery where the reconstruction of complex and sensitive anatomic structures is routine following the resection of large and/or invasive tumors. Successful flap surgery results in tissue that is sufficiently perfused with both blood and extracellular water. If insufficient fluid levels are maintained, the flap tissue becomes necrotic and must be excised immediately to prevent infection developing and spreading to the surrounding areas. The goal of this work is to investigate the hydration of surgical flaps and correlate image features to successful graft outcomes. Advancement flaps were created on the abdomens of rat models. One rat model was labeled control and care was taken to ensure a successful flap outcome. The flap on the second rat was compromised with restricted blood flow and allowed to fail. The flaps of both rats were imaged once a day over the course of a week at which point the compromised flap had begun to show signs of necrosis. Significant differences in tissue water content were observed between rats over the experimental period. The results suggest that THz imaging may enable early assessment of flap viability.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"65 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131647313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seoho Lee, Dakota O'Dell, Jess Hohenstein, S. Colt, S. Mehta, D. Erickson
Vitamin B12 deficiency is the leading cause of cognitive decline in the elderly and is associated with increased risks of several acute and chronic conditions including anemia. The deficiency is prevalent among the world population, most of whom are unaware of their condition due to the lack of a simple diagnostics system. Recent advancements in the smartphone-enabled mobile health can help address this problem by making the deficiency tests more accessible. Previously, our group has demonstrated the NutriPhone, a smartphone platform for the accurate quantification of vitamin D levels. The NutriPhone technology comprises of a disposable test strip that performs a colorimetric reaction upon collecting a sample, a reusable accessory that interfaces with the smartphone camera, and a smartphone app that stores the algorithm for analyzing the test-strip reaction. In this work, we show that the NutriPhone can be expanded to measure vitamin B12 concentrations by developing a lateral flow assay for B12 that is compatible with our NutriPhone system. Our novel vitamin B12 assay incorporates blood sample processing and key reagent storage on-chip, which advances it into a sample-in-answer-out format that is suitable for point-of-care diagnostic applications. In order to enable the detection of pM levels of vitamin B12 levels, silver amplification of the initial signal is used within the total assay time of less than 15 minutes. We demonstrate the effectiveness of our NutriPhone system by deploying it in a resource-limited clinical setting in India where it is used to test tens of participants for vitamin B12 deficiency.
{"title":"NutriPhone: vitamin B12 testing on your smartphone (Conference Presentation)","authors":"Seoho Lee, Dakota O'Dell, Jess Hohenstein, S. Colt, S. Mehta, D. Erickson","doi":"10.1117/12.2210761","DOIUrl":"https://doi.org/10.1117/12.2210761","url":null,"abstract":"Vitamin B12 deficiency is the leading cause of cognitive decline in the elderly and is associated with increased risks of several acute and chronic conditions including anemia. The deficiency is prevalent among the world population, most of whom are unaware of their condition due to the lack of a simple diagnostics system. Recent advancements in the smartphone-enabled mobile health can help address this problem by making the deficiency tests more accessible. Previously, our group has demonstrated the NutriPhone, a smartphone platform for the accurate quantification of vitamin D levels. The NutriPhone technology comprises of a disposable test strip that performs a colorimetric reaction upon collecting a sample, a reusable accessory that interfaces with the smartphone camera, and a smartphone app that stores the algorithm for analyzing the test-strip reaction. In this work, we show that the NutriPhone can be expanded to measure vitamin B12 concentrations by developing a lateral flow assay for B12 that is compatible with our NutriPhone system. Our novel vitamin B12 assay incorporates blood sample processing and key reagent storage on-chip, which advances it into a sample-in-answer-out format that is suitable for point-of-care diagnostic applications. In order to enable the detection of pM levels of vitamin B12 levels, silver amplification of the initial signal is used within the total assay time of less than 15 minutes. We demonstrate the effectiveness of our NutriPhone system by deploying it in a resource-limited clinical setting in India where it is used to test tens of participants for vitamin B12 deficiency.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"9699 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131344897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenbo Wang, S. Feng, I. Tai, Guannan Chen, Rong Chen, H. Zeng
Colorectal cancer (CRC) is the third most common type of cancer and forth leading cause of cancer-related death. Early diagnosis is the key to long-term patient survival. Programmatic screening for the general population has shown to be cost-effective in reducing the incidence and mortality from CRC. Current CRC screening strategy relies on a broad range of test techniques such as fecal based tests and endoscopic exams. Occult blood tests like fecal immunochemical test is a cost effective way to detect CRC but have limited diagnostic values in detecting adenomatous polyp, the most treatable precursor to CRC. In the present work, we proposed the use of surface enhanced Raman spectroscopy (SERS) with silver nanoparticles as substrate to analyze blood plasma for detecting both CRC and adenomatous polyps. Blood plasma samples collected from healthy subjects and patients diagnosed with adenomas and CRC were prepared with nanoparticles and measured using a real-time fiber optic probe based Raman system. The collected SERS spectra are analyzed with partial least squares-discriminant analysis. Classification of normal versus CRC plus adenomatous polyps achieved diagnostic sensitivity of 86.4% and specificity of 80%. This exploratory study suggests that blood plasma SERS analysis has potential to become a screening test for detecting both CRC and adenomas.
{"title":"Blood test using surface-enhanced Raman spectroscopy with colloidal silver nanoparticle substrate to detect polyps and colorectal cancer (Conference Presentation)","authors":"Wenbo Wang, S. Feng, I. Tai, Guannan Chen, Rong Chen, H. Zeng","doi":"10.1117/12.2211419","DOIUrl":"https://doi.org/10.1117/12.2211419","url":null,"abstract":"Colorectal cancer (CRC) is the third most common type of cancer and forth leading cause of cancer-related death. Early diagnosis is the key to long-term patient survival. Programmatic screening for the general population has shown to be cost-effective in reducing the incidence and mortality from CRC. Current CRC screening strategy relies on a broad range of test techniques such as fecal based tests and endoscopic exams. Occult blood tests like fecal immunochemical test is a cost effective way to detect CRC but have limited diagnostic values in detecting adenomatous polyp, the most treatable precursor to CRC. In the present work, we proposed the use of surface enhanced Raman spectroscopy (SERS) with silver nanoparticles as substrate to analyze blood plasma for detecting both CRC and adenomatous polyps. Blood plasma samples collected from healthy subjects and patients diagnosed with adenomas and CRC were prepared with nanoparticles and measured using a real-time fiber optic probe based Raman system. The collected SERS spectra are analyzed with partial least squares-discriminant analysis. Classification of normal versus CRC plus adenomatous polyps achieved diagnostic sensitivity of 86.4% and specificity of 80%. This exploratory study suggests that blood plasma SERS analysis has potential to become a screening test for detecting both CRC and adenomas.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125225969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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