Pin-Chieh Huang, M. Marjanovic, D. Spillman, Boris M. Odintsov, S. Boppart
Magnetic nanoparticles (MNPs) have been utilized in magnetic hyperthermia to treat solid tumors. Under an appropriate AC magnetic field, energy can be transferred to the MNPs to heat up the intended tissue target while sparing non-targeted healthy tissue. However, a sensitive monitoring technique for the dose of MNP thermal therapy is desirable in order to prevent over-treatment and collateral injury. Typical hyperthermia dosimetry often relies on changes in imaging properties or temperature measurements based on the thermal distribution. Alternative dosimetric indicators can include the biomechanical properties of the tissue, reflecting the changes due to protein denaturation, coagulation, and tissue dehydration during hyperthermia treatments. Tissue stiffness can be probed by elastography modalities including MRI, ultrasound imaging, and optical coherence elastography (OCE), with OCE showing the highest displacement sensitivity (tens of nanometers). Magnetomotive optical coherence elastography (MM-OCE) is one type of OCE that utilizes MNPs as internal force transducers to probe the tissue stiffness. Therefore, we examined the feasibility of evaluating the hyperthermia dose based on the elasticity changes revealed by MM-OCE. Superparamagnetic MNPs were applied to ex vivo tissue specimens for both magnetic hyperthermia and MM-OCE experiments, where temperature and elastic modulus were obtained. A correlation between temperature rise and measured stiffness was observed. In addition, we found that with repetitive sequential treatments, tissue stiffness increased, while temperature rise remained relatively constant. These results potentially suggest that MM-OCE could indicate the irreversible changes the tissue undergoes during thermal therapy, which supports the idea for MM-OCE-based hyperthermia dosage control in future applications.
{"title":"Magnetic hyperthermia dosimetry by biomechanical properties revealed in magnetomotive optical coherence elastography (MM-OCE) (Conference Presentation)","authors":"Pin-Chieh Huang, M. Marjanovic, D. Spillman, Boris M. Odintsov, S. Boppart","doi":"10.1117/12.2213198","DOIUrl":"https://doi.org/10.1117/12.2213198","url":null,"abstract":"Magnetic nanoparticles (MNPs) have been utilized in magnetic hyperthermia to treat solid tumors. Under an appropriate AC magnetic field, energy can be transferred to the MNPs to heat up the intended tissue target while sparing non-targeted healthy tissue. However, a sensitive monitoring technique for the dose of MNP thermal therapy is desirable in order to prevent over-treatment and collateral injury. Typical hyperthermia dosimetry often relies on changes in imaging properties or temperature measurements based on the thermal distribution. Alternative dosimetric indicators can include the biomechanical properties of the tissue, reflecting the changes due to protein denaturation, coagulation, and tissue dehydration during hyperthermia treatments. Tissue stiffness can be probed by elastography modalities including MRI, ultrasound imaging, and optical coherence elastography (OCE), with OCE showing the highest displacement sensitivity (tens of nanometers). Magnetomotive optical coherence elastography (MM-OCE) is one type of OCE that utilizes MNPs as internal force transducers to probe the tissue stiffness. Therefore, we examined the feasibility of evaluating the hyperthermia dose based on the elasticity changes revealed by MM-OCE. Superparamagnetic MNPs were applied to ex vivo tissue specimens for both magnetic hyperthermia and MM-OCE experiments, where temperature and elastic modulus were obtained. A correlation between temperature rise and measured stiffness was observed. In addition, we found that with repetitive sequential treatments, tissue stiffness increased, while temperature rise remained relatively constant. These results potentially suggest that MM-OCE could indicate the irreversible changes the tissue undergoes during thermal therapy, which supports the idea for MM-OCE-based hyperthermia dosage control in future applications.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"58 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124882996","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}
Despite considerable advances in guidance of radiofrequency ablation (RFA) therapies for atrial fibrillation, success rates have been hampered by an inability to intraoperatively characterize the extent of permanent injury. Insufficient lesions can elusively create transient conduction blockages that eventually reconduct. Prior studies suggest significantly greater met-myoglobin (Mmb) concentrations in the lesion core than those in the healthy myocardium and may serve as a marker for irreversible tissue damage. In this work, we present real-time monitoring of permanent injury through spectroscopic assessment of Mmb concentrations at the catheter tip. Atrial wedges (n=6) were excised from four fresh swine hearts and submerged under pulsatile flow of warm (37oC) phosphate buffered saline. A commercial RFA catheter inserted into a fiber optic sheath allowed for simultaneous measurement of tissue diffuse reflectance (DR) spectra (500-650nm) during application of RF energy. Optical measurements were continuously acquired before, during, and post-ablation, in addition to healthy neighboring tissue. Met-myoglobin, oxy-myoglobin, and deoxy-myoglobin concentrations were extracted from each spectrum using an inverse Monte Carlo method. Tissue injury was validated with Masson’s trichrome and hematoxylin and eosin staining. Time courses revealed a rapid increase in tissue Mmb concentrations at the onset of RFA treatment and a gradual plateauing thereafter. Extracted Mmb concentrations were significantly greater post-ablation (p<0.0001) as compared to healthy tissue and correlated well with histological assessment of severe thermal tissue destruction. On going studies are aimed at integrating these findings with prior work on near infrared spectroscopic lesion depth assessment. These results support the use of spectroscopy-facilitated guidance of RFA therapies for real-time permanent injury estimation.
{"title":"Real-time optical monitoring of permanent lesion progression in radiofrequency ablated cardiac tissue (Conference Presentation)","authors":"Rajinder P. Singh-Moon, C. Hendon","doi":"10.1117/12.2212062","DOIUrl":"https://doi.org/10.1117/12.2212062","url":null,"abstract":"Despite considerable advances in guidance of radiofrequency ablation (RFA) therapies for atrial fibrillation, success rates have been hampered by an inability to intraoperatively characterize the extent of permanent injury. Insufficient lesions can elusively create transient conduction blockages that eventually reconduct. Prior studies suggest significantly greater met-myoglobin (Mmb) concentrations in the lesion core than those in the healthy myocardium and may serve as a marker for irreversible tissue damage. In this work, we present real-time monitoring of permanent injury through spectroscopic assessment of Mmb concentrations at the catheter tip. Atrial wedges (n=6) were excised from four fresh swine hearts and submerged under pulsatile flow of warm (37oC) phosphate buffered saline. A commercial RFA catheter inserted into a fiber optic sheath allowed for simultaneous measurement of tissue diffuse reflectance (DR) spectra (500-650nm) during application of RF energy. Optical measurements were continuously acquired before, during, and post-ablation, in addition to healthy neighboring tissue. Met-myoglobin, oxy-myoglobin, and deoxy-myoglobin concentrations were extracted from each spectrum using an inverse Monte Carlo method. Tissue injury was validated with Masson’s trichrome and hematoxylin and eosin staining. Time courses revealed a rapid increase in tissue Mmb concentrations at the onset of RFA treatment and a gradual plateauing thereafter. Extracted Mmb concentrations were significantly greater post-ablation (p<0.0001) as compared to healthy tissue and correlated well with histological assessment of severe thermal tissue destruction. On going studies are aimed at integrating these findings with prior work on near infrared spectroscopic lesion depth assessment. These results support the use of spectroscopy-facilitated guidance of RFA therapies for real-time permanent injury estimation.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124883198","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. Gora, Leigh H. Simmons, Aubrey R. Tiernan, Catriona N. Grant, Amna R. Soomro, Elizabeth Walker Corkery, M. Rosenberg, J. Metlay, G. Tearney
We have developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires microscopic images of the entire esophagus in unsedated subjects in a quick and comfortable procedure. To test its capabilities of TCE to become a population-based screening device, we conducted a clinical feasibility study in the primary care office. The swept-source OCT imaging system (1310nm central wavelength, 40kHz A-line rate, 10um axial resolution) together with the tethered capsule catheter (11x25mm capsule attached to a flexible tether) were transferred to the PCP office where unsedated patients scheduled for non-urgent PCP visits swallowed the capsule and microscopic OCT images of the entire esophagus were collected. After the whole length of the esophagus was imaged, the catheter was disinfected for reuse. Twenty subjects were enrolled in the study, including nine female and eleven male. All TCE procedures were performed by a nurse and lasted in average 5:42 ± 1:54 min. High-resolution images of the esophagus were obtained in all seventeen subjects that swallowed the capsule. Our clinical experience in this cohort, subject feedback, image quality, and technological adaptations for efficient utilization in this setting will be presented. The ease and simplicity of the procedure combined with high quality of the images demonstrate the potential for this technology to become a population-based screening device. Technology limitations and future development guided by findings from this initial experience will be discussed with the goal of effectively translating TCE to the outpatient primary care setting.
{"title":"Tethered capsule OCT endomicroscopy: from bench to bedside at the primary care office (Conference Presentation)","authors":"M. Gora, Leigh H. Simmons, Aubrey R. Tiernan, Catriona N. Grant, Amna R. Soomro, Elizabeth Walker Corkery, M. Rosenberg, J. Metlay, G. Tearney","doi":"10.1117/12.2211393","DOIUrl":"https://doi.org/10.1117/12.2211393","url":null,"abstract":"We have developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires microscopic images of the entire esophagus in unsedated subjects in a quick and comfortable procedure. To test its capabilities of TCE to become a population-based screening device, we conducted a clinical feasibility study in the primary care office. The swept-source OCT imaging system (1310nm central wavelength, 40kHz A-line rate, 10um axial resolution) together with the tethered capsule catheter (11x25mm capsule attached to a flexible tether) were transferred to the PCP office where unsedated patients scheduled for non-urgent PCP visits swallowed the capsule and microscopic OCT images of the entire esophagus were collected. After the whole length of the esophagus was imaged, the catheter was disinfected for reuse. Twenty subjects were enrolled in the study, including nine female and eleven male. All TCE procedures were performed by a nurse and lasted in average 5:42 ± 1:54 min. High-resolution images of the esophagus were obtained in all seventeen subjects that swallowed the capsule. Our clinical experience in this cohort, subject feedback, image quality, and technological adaptations for efficient utilization in this setting will be presented. The ease and simplicity of the procedure combined with high quality of the images demonstrate the potential for this technology to become a population-based screening device. Technology limitations and future development guided by findings from this initial experience will be discussed with the goal of effectively translating TCE to the outpatient primary care setting.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129410196","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}
A. Ponticorvo, Rebecca Rowland, Melissa L. Baldado, G. Kennedy, R. Saager, Bernard Choi, Anthony J. Durkin
The ability to accurately assess burn wound severity in a timely manner is a critical component of wound management as it dictates the course of treatment. While full thickness and superficial burns can be easily diagnosed through visual inspection, burns that fall in between these categories are difficult to classify. Additionally, the ability to better quantify different stages of wound healing from a burn of any severity would be important for evaluating the efficacy of different treatment options. Here we present a longitudinal (28 day) study that employs spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) as non-invasive technologies to characterize in-vivo burn wounds and healing in a murine model. Burn wounds were created using an established technique of a brass comb heated to a given temperature and applied for a set amount of time. They were imaged immediately after the initial injury and then at 2, 4, 7, 14, 21, and 28 days following the injury. Biopsies were taken on the day of the injury in order to verify the extent of the burn damage as well as at different time points after the injury in order to visualize different stages of inflammation and healing. The results of this study suggest that the reduced scattering coefficient measured using SFDI and blood flow as measured using LSI have the potential to provide useful metrics for quantifying the severity of burn injuries as well as track the different stages associated with wound healing progression.
{"title":"Quantitative long term measurements of burns in a rat model using spatial frequency domain imaging and laser speckle imaging (Conference Presentation)","authors":"A. Ponticorvo, Rebecca Rowland, Melissa L. Baldado, G. Kennedy, R. Saager, Bernard Choi, Anthony J. Durkin","doi":"10.1117/12.2214080","DOIUrl":"https://doi.org/10.1117/12.2214080","url":null,"abstract":"The ability to accurately assess burn wound severity in a timely manner is a critical component of wound management as it dictates the course of treatment. While full thickness and superficial burns can be easily diagnosed through visual inspection, burns that fall in between these categories are difficult to classify. Additionally, the ability to better quantify different stages of wound healing from a burn of any severity would be important for evaluating the efficacy of different treatment options. Here we present a longitudinal (28 day) study that employs spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) as non-invasive technologies to characterize in-vivo burn wounds and healing in a murine model. Burn wounds were created using an established technique of a brass comb heated to a given temperature and applied for a set amount of time. They were imaged immediately after the initial injury and then at 2, 4, 7, 14, 21, and 28 days following the injury. Biopsies were taken on the day of the injury in order to verify the extent of the burn damage as well as at different time points after the injury in order to visualize different stages of inflammation and healing. The results of this study suggest that the reduced scattering coefficient measured using SFDI and blood flow as measured using LSI have the potential to provide useful metrics for quantifying the severity of burn injuries as well as track the different stages associated with wound healing progression.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129871741","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}
X. Deán‐Ben, V. Ermolayev, S. Mandal, V. Ntziachristos, D. Razansky
Imaging plays an increasingly important role in clinical management and preclinical studies of cancer. Application of optical molecular imaging technologies, in combination with highly specific contrast agent approaches, eminently contributed to understanding of functional and histological properties of tumors and anticancer therapies. Yet, optical imaging exhibits deterioration in spatial resolution and other performance metrics due to light scattering in deep living tissues. High resolution molecular imaging at the whole-organ or whole-body scale may therefore bring additional understanding of vascular networks, blood perfusion and microenvironment gradients of malignancies. In this work, we constructed a volumetric multispectral optoacoustic tomography (vMSOT) scanner for cancer imaging in preclinical models and explored its capacity for real-time 3D intravital imaging of whole breast cancer allografts in mice. Intrinsic tissue properties, such as blood oxygenation gradients, along with the distribution of externally administered liposomes carrying clinically-approved indocyanine green dye (lipo-ICG) were visualized in order to study vascularization, probe penetration and extravasation kinetics in different regions of interest within solid tumors. The use of v-MSOT along with the application of volumetric image analysis and perfusion tracking tools for studies of pathophysiological processes within microenvironment gradients of solid tumors demonstrated superior volumetric imaging system performance with sustained competitive resolution and imaging depth suitable for investigations in preclinical cancer models.
{"title":"Four dimensional optoacoustic imaging of perfusion in preclinical breast tumor model in vivo (Conference Presentation)","authors":"X. Deán‐Ben, V. Ermolayev, S. Mandal, V. Ntziachristos, D. Razansky","doi":"10.1117/12.2213112","DOIUrl":"https://doi.org/10.1117/12.2213112","url":null,"abstract":"Imaging plays an increasingly important role in clinical management and preclinical studies of cancer. Application of optical molecular imaging technologies, in combination with highly specific contrast agent approaches, eminently contributed to understanding of functional and histological properties of tumors and anticancer therapies. Yet, optical imaging exhibits deterioration in spatial resolution and other performance metrics due to light scattering in deep living tissues. High resolution molecular imaging at the whole-organ or whole-body scale may therefore bring additional understanding of vascular networks, blood perfusion and microenvironment gradients of malignancies. In this work, we constructed a volumetric multispectral optoacoustic tomography (vMSOT) scanner for cancer imaging in preclinical models and explored its capacity for real-time 3D intravital imaging of whole breast cancer allografts in mice. Intrinsic tissue properties, such as blood oxygenation gradients, along with the distribution of externally administered liposomes carrying clinically-approved indocyanine green dye (lipo-ICG) were visualized in order to study vascularization, probe penetration and extravasation kinetics in different regions of interest within solid tumors. The use of v-MSOT along with the application of volumetric image analysis and perfusion tracking tools for studies of pathophysiological processes within microenvironment gradients of solid tumors demonstrated superior volumetric imaging system performance with sustained competitive resolution and imaging depth suitable for investigations in preclinical cancer models.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128327357","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}
Esophageal squamous cell neoplasia (ESCN) is the sixth leading cause of cancer death worldwide. Most deaths due to ESCN occur in developing countries, with highest risk areas in northern China. Lugol’s chromoendoscopy (LCE) is the gold-standard for ESCN screening; while the sensitivity of LCE for ESCN is >95%, LCE suffers poor specificity (< 65%) due to false positive findings from inflammatory lesions. High resolution microendoscopy (HRME) uses a low-cost, fiber-optic fluorescence microscope to image morphology of the surface epithelium without need for biopsy. We developed a tablet-interfaced HRME with automated, real-time image analysis. In an in vivo study of 177 patients referred for endoscopy in China, use of the algorithm identified neoplasia with a sensitivity and specificity of 95% and 91% compared to the gold standard of histology.
{"title":"High resolution microendoscopy for early detection of esophageal cancer in low-resource settings (Conference Presentation)","authors":"R. Richards-Kortum","doi":"10.1117/12.2229789","DOIUrl":"https://doi.org/10.1117/12.2229789","url":null,"abstract":"Esophageal squamous cell neoplasia (ESCN) is the sixth leading cause of cancer death worldwide. Most deaths due to ESCN occur in developing countries, with highest risk areas in northern China. Lugol’s chromoendoscopy (LCE) is the gold-standard for ESCN screening; while the sensitivity of LCE for ESCN is >95%, LCE suffers poor specificity (< 65%) due to false positive findings from inflammatory lesions. High resolution microendoscopy (HRME) uses a low-cost, fiber-optic fluorescence microscope to image morphology of the surface epithelium without need for biopsy. We developed a tablet-interfaced HRME with automated, real-time image analysis. In an in vivo study of 177 patients referred for endoscopy in China, use of the algorithm identified neoplasia with a sensitivity and specificity of 95% and 91% compared to the gold standard of histology.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"58 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128715293","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}
Jing Dong, M. Gora, R. Reddy, W. Trasischker, Oriane Poupart, Weina Lu, R. Carruth, Catriona N. Grant, Amna R. Soomro, Aubrey R. Tiernan, M. Rosenberg, N. Nishioka, G. Tearney
While endoscopy is the most commonly used modality for diagnosing upper GI tract disease, this procedure usually requires patient sedation that increases cost and mandates its operation in specialized settings. In addition, endoscopy only visualizes tissue superfically at the macroscopic scale, which is problematic for many diseases that manifest below the surface at a microscopic scale. Our lab has previously developed technology termed tethered capsule OCT endomicroscopy (TCE) to overcome these diagnostic limitations of endoscopy. The TCE device is a swallowable capsule that contains optomechanical components that circumferentially scan the OCT beam inside the body as the pill traverses the organ via peristalsis. While we have successfully imaged ~100 patients with the TCE device, the optics of our current device have many elements and are complex, comprising a glass ferrule, optical fiber, glass spacer, GRIN lens and prism. As we scale up manufacturing of this device for clinical translation, we must decrease the cost and improve the manufacturability of the capsule’s optical configuration. In this abstract, we report on the design and development of simplificed TCE optics that replace the GRIN lens-based configuration with an angle-polished ball lens design. The new optics include a single mode optical fiber, a glass spacer and an angle polished ball lens, that are all fusion spliced together. The ball lens capsule has resolutions that are comparable with those of our previous GRIN lens configuration (30µm (lateral) × 7 µm (axial)). Results in human subjects show that OCT-based TCE using the ball lens not only provides rapid, high quality microstructural images of upper GI tract, but also makes it possible to implement this technology inexpensively and on a larger scale.
{"title":"Tethered capsule OCT endomicroscopy for upper gastrointestinal tract imaging by using ball lens probe (Conference Presentation)","authors":"Jing Dong, M. Gora, R. Reddy, W. Trasischker, Oriane Poupart, Weina Lu, R. Carruth, Catriona N. Grant, Amna R. Soomro, Aubrey R. Tiernan, M. Rosenberg, N. Nishioka, G. Tearney","doi":"10.1117/12.2213931","DOIUrl":"https://doi.org/10.1117/12.2213931","url":null,"abstract":"While endoscopy is the most commonly used modality for diagnosing upper GI tract disease, this procedure usually requires patient sedation that increases cost and mandates its operation in specialized settings. In addition, endoscopy only visualizes tissue superfically at the macroscopic scale, which is problematic for many diseases that manifest below the surface at a microscopic scale. Our lab has previously developed technology termed tethered capsule OCT endomicroscopy (TCE) to overcome these diagnostic limitations of endoscopy. The TCE device is a swallowable capsule that contains optomechanical components that circumferentially scan the OCT beam inside the body as the pill traverses the organ via peristalsis. While we have successfully imaged ~100 patients with the TCE device, the optics of our current device have many elements and are complex, comprising a glass ferrule, optical fiber, glass spacer, GRIN lens and prism. As we scale up manufacturing of this device for clinical translation, we must decrease the cost and improve the manufacturability of the capsule’s optical configuration. In this abstract, we report on the design and development of simplificed TCE optics that replace the GRIN lens-based configuration with an angle-polished ball lens design. The new optics include a single mode optical fiber, a glass spacer and an angle polished ball lens, that are all fusion spliced together. The ball lens capsule has resolutions that are comparable with those of our previous GRIN lens configuration (30µm (lateral) × 7 µm (axial)). Results in human subjects show that OCT-based TCE using the ball lens not only provides rapid, high quality microstructural images of upper GI tract, but also makes it possible to implement this technology inexpensively and on a larger scale.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"9691 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129830250","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}
Focusing light deep inside scattering media plays a key role in such biomedical applications as high resolution optical imaging, control, and therapy. In recent years, wavefront shaping technologies have come a long way in controlling light propagation in complex media. A prominent example is time-reversed ultrasonically encoded (TRUE) focusing, which allows noninvasive introduction of “guide stars” inside biological tissue to guide light focusing. By measuring the optical wavefront emanating from an ultrasound focus created at the target location, TRUE determines the desired wavefront non-iteratively, and achieves focusing at the target position via a subsequent optical time reversal. Compared to digital counterparts that employ slow electronic spatial light modulators and cameras, analog TRUE focusing relies on nonlinear photorefractive crystals that inherently accommodate more spatial modes and eliminate the troublesome alignment and data transfer required by digital approaches. However, analog TRUE focusing suffers from its small gain, defined as the energy or power ratio between the focusing and probing beams in the focal volume. Here, by implementing a modified analog TRUE focusing scheme that squeezes the duration of the time-reversed photon packet below the carrier-recombination-limited hologram decay time of the crystal, we demonstrated a photon flux amplification much greater than unity at a preset focal voxel in between two scattering layers. Although the energy gain was still below unity, the unprecedented power gain will nevertheless benefit new biomedical applications.
{"title":"Analog time-reversed ultrasonically encoded (TRUE) optical focusing inside scattering media with high power gain (Conference Presentation)","authors":"Cheng Ma, Xiao Xu, Lihong V. Wang","doi":"10.1117/12.2209396","DOIUrl":"https://doi.org/10.1117/12.2209396","url":null,"abstract":"Focusing light deep inside scattering media plays a key role in such biomedical applications as high resolution optical imaging, control, and therapy. In recent years, wavefront shaping technologies have come a long way in controlling light propagation in complex media. A prominent example is time-reversed ultrasonically encoded (TRUE) focusing, which allows noninvasive introduction of “guide stars” inside biological tissue to guide light focusing. By measuring the optical wavefront emanating from an ultrasound focus created at the target location, TRUE determines the desired wavefront non-iteratively, and achieves focusing at the target position via a subsequent optical time reversal. Compared to digital counterparts that employ slow electronic spatial light modulators and cameras, analog TRUE focusing relies on nonlinear photorefractive crystals that inherently accommodate more spatial modes and eliminate the troublesome alignment and data transfer required by digital approaches. However, analog TRUE focusing suffers from its small gain, defined as the energy or power ratio between the focusing and probing beams in the focal volume. Here, by implementing a modified analog TRUE focusing scheme that squeezes the duration of the time-reversed photon packet below the carrier-recombination-limited hologram decay time of the crystal, we demonstrated a photon flux amplification much greater than unity at a preset focal voxel in between two scattering layers. Although the energy gain was still below unity, the unprecedented power gain will nevertheless benefit new biomedical applications.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"196 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122352362","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}
A number of disease conditions including coronary atherosclerosis, peripheral artery disease and gastro-intestinal malignancies are associated with alterations in tissue mechanical properties. Laser speckle rheology (LSR) has been demonstrated to provide important information on tissue mechanical properties by analyzing the time scale of temporal speckle intensity fluctuations, which serves as an index of tissue viscoelasticity. In order to measure the mechanical properties of luminal organs in vivo, LSR must be conducted via a miniature endoscope or catheter. Here we demonstrate the capability of an omni-directional LSR catheter to quantify tissue mechanical properties over the entire luminal circumference without the need for rotational motion. Retracting the catheter using a motor-drive assembly enables the reconstruction of cylindrical maps of tissue mechanical properties. The performance of the LSR catheter is tested using a luminal phantom with mechanical moduli that vary in both circumferential and longitudinal directions. 2D cylindrical maps of phantom viscoelastic properties are reconstructed over four quadrants of the coronary circumference simultaneously during catheter pullback. The reconstructed cylindrical maps of the decorrelation time constants easily distinguish the different gel components of the phantom with different viscoelastic moduli. The average values of decorrelation times calculated for each gel component of the phantom show a strong correspondence with the viscoelastic moduli measured via standard mechanical rheometry. These results highlight the capability for cylindrical mapping of tissue viscoelastic properties using LSR in luminal organs using a miniature catheter, thus opening the opportunity for improved diagnosis of several disease conditions.
{"title":"Intraluminal mapping of tissue viscoelastic properties using laser speckle rheology catheter (Conference Presentation)","authors":"Jing Wang, M. Hosoda, D. Tshikudi, S. Nadkarni","doi":"10.1117/12.2213207","DOIUrl":"https://doi.org/10.1117/12.2213207","url":null,"abstract":"A number of disease conditions including coronary atherosclerosis, peripheral artery disease and gastro-intestinal malignancies are associated with alterations in tissue mechanical properties. Laser speckle rheology (LSR) has been demonstrated to provide important information on tissue mechanical properties by analyzing the time scale of temporal speckle intensity fluctuations, which serves as an index of tissue viscoelasticity. In order to measure the mechanical properties of luminal organs in vivo, LSR must be conducted via a miniature endoscope or catheter. Here we demonstrate the capability of an omni-directional LSR catheter to quantify tissue mechanical properties over the entire luminal circumference without the need for rotational motion. Retracting the catheter using a motor-drive assembly enables the reconstruction of cylindrical maps of tissue mechanical properties. The performance of the LSR catheter is tested using a luminal phantom with mechanical moduli that vary in both circumferential and longitudinal directions. 2D cylindrical maps of phantom viscoelastic properties are reconstructed over four quadrants of the coronary circumference simultaneously during catheter pullback. The reconstructed cylindrical maps of the decorrelation time constants easily distinguish the different gel components of the phantom with different viscoelastic moduli. The average values of decorrelation times calculated for each gel component of the phantom show a strong correspondence with the viscoelastic moduli measured via standard mechanical rheometry. These results highlight the capability for cylindrical mapping of tissue viscoelastic properties using LSR in luminal organs using a miniature catheter, thus opening the opportunity for improved diagnosis of several disease conditions.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"9710 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130712475","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}
Xiaoming Wei, Sisi Tan, A. Mussot, A. Kudlinski, K. Tsia, K. Wong
Fiber optical parametric amplifier (FOPA) has gained its popularity in the telecommunication systems at the 1.5-um window for its gain, bandwidth etc. Unfortunately, its practical application at the bio-favorable window, i.e. 1.0 um, still requires substantial efforts. Thus, here we report a versatile all-fiber optical parametric amplifier for life-science (OPALS) at 1.0 um as an add-on module for optical imaging system. The parametric gain fiber (photonic-crystal fiber (PCF), 110 m in length) is specially designed to reduce the longitudinal dispersion fluctuation, which yields a superior figure of merit, i.e. a total insertion loss of ~2.5 dB and a nonlinear coefficient of 34 /(W•km). Our OPALS delivers a superior performance in terms of gain (~158,000), bandwidth (>100 nm) and gain flatness (< 3-dB ripple). Experimentally, we show that: 1) a wavelength-varying quasi-monochrome pump achieves a 52-dB gain and 160-nm bandwidth, but at the expense of a larger gain-spectrum ripple, i.e. a bell-shaped; 2) the birefringence of the parametric gain medium, i.e. PCF in this case, can be utilized to improve the gain-spectrum flatness of OPALS by 10.5 dB, meanwhile a 100-nm bandwidth can be guaranteed; 3) the gain-spectrum flatness of OPALS can be further flattened by using a high-speed wavelength-sweeping pump, which exhibits a 110-nm flat gain spectrum with ripple less than 3 dB. Finally, we employ this versatile all-fiber OPALS as an add-on module to enhance the sensitivity of a spectrally-encoded microscope by 47 dB over an ultra-wide spectral range.
{"title":"Ultra-wideband fiber optical parametric amplifier for spectrally-encoded microscopy (Conference Presentation)","authors":"Xiaoming Wei, Sisi Tan, A. Mussot, A. Kudlinski, K. Tsia, K. Wong","doi":"10.1117/12.2210811","DOIUrl":"https://doi.org/10.1117/12.2210811","url":null,"abstract":"Fiber optical parametric amplifier (FOPA) has gained its popularity in the telecommunication systems at the 1.5-um window for its gain, bandwidth etc. Unfortunately, its practical application at the bio-favorable window, i.e. 1.0 um, still requires substantial efforts. Thus, here we report a versatile all-fiber optical parametric amplifier for life-science (OPALS) at 1.0 um as an add-on module for optical imaging system. The parametric gain fiber (photonic-crystal fiber (PCF), 110 m in length) is specially designed to reduce the longitudinal dispersion fluctuation, which yields a superior figure of merit, i.e. a total insertion loss of ~2.5 dB and a nonlinear coefficient of 34 /(W•km). Our OPALS delivers a superior performance in terms of gain (~158,000), bandwidth (>100 nm) and gain flatness (< 3-dB ripple). Experimentally, we show that: 1) a wavelength-varying quasi-monochrome pump achieves a 52-dB gain and 160-nm bandwidth, but at the expense of a larger gain-spectrum ripple, i.e. a bell-shaped; 2) the birefringence of the parametric gain medium, i.e. PCF in this case, can be utilized to improve the gain-spectrum flatness of OPALS by 10.5 dB, meanwhile a 100-nm bandwidth can be guaranteed; 3) the gain-spectrum flatness of OPALS can be further flattened by using a high-speed wavelength-sweeping pump, which exhibits a 110-nm flat gain spectrum with ripple less than 3 dB. Finally, we employ this versatile all-fiber OPALS as an add-on module to enhance the sensitivity of a spectrally-encoded microscope by 47 dB over an ultra-wide spectral range.","PeriodicalId":227483,"journal":{"name":"SPIE BiOS","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132876449","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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