Application of Ultrasound Thermal Imaging for Monitoring Laser Ablation in Ex Vivo Cardiac Tissue.

BACKGROUND AND OBJECTIVE: Laser ablation can be used to treat atrial fibrillation by thermally isolating pulmonary veins. In this study, we evaluated the feasibility of high-resolution (<1 mm) ultrasound thermal imaging to monitor spatial temperature distribution during laser ablation on ex vivo cardiac tissue. STUDY DESIGN/MATERIALS AND METHODS: Laser ablation (808 nm) was performed on five porcine cardiac tissue samples. A thermocouple was used to measure the interstitial tissue temperature during the laser ablation process. Tissue-strain-based ultrasound thermal imaging was conducted to monitor the spatial distribution of the temperature in the cardiac tissue. The tissue temperature was estimated from the time shifts of ultrasound signals owing to the changes in the speed of sound and was compared with the measured temperature. The temperature estimation coefficient k of porcine cardiac tissue was calculated from the estimated thermal strain and the measured temperature. The degree of tissue coagulation (temperatures > 50°C) was derived from the estimated temperature and was compared with that of the tested cardiac tissue. RESULTS: The estimated tissue temperature using strain-based ultrasound thermal imaging at a depth of 1 mm agreed with thermocouple measurements. During the 30-second period of the laser ablation process, the estimated tissue temperature increased from 25 to 70°C at a depth of 0.1 mm, while the estimated temperature at a depth of 1 mm increased up to 46°C. Owing to the uncertainty of the coefficient k, the k value of the porcine cardiac tissue varied from 160 to 220°C with temperature changes of up to 20°C. The estimated coagulation region in the ultrasound thermal imaging was 20% wider (+0.6 mm) but 9% shallower (-0.1 mm) than the measured region of the ablated porcine cardiac tissue. CONCLUSIONS: The current study demonstrated the feasibility of temperature monitoring with the use of ultrasound thermal imaging during the laser ablation on ex vivo porcine cardiac tissue. The high-resolution ultrasound thermal imaging could map the spatial distribution of the tissue temperature. The proposed method can be used to monitor the temperature and thermal coagulation to achieve effective laser ablation for atrial fibrillation. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Preliminary study of optical coherence tomography imaging to identify microscopic extrathyroidal extension in patients with papillary thyroid carcinoma.

BACKGROUND AND OBJECTIVES: We evaluated the feasibility of using optical coherence tomography (OCT), to identify microscopic extrathyroidal extension (mETE) in ex vivo thyroidectomy specimens of patients who underwent thyroidectomy for the treatment of papillary thyroid carcinoma (PTC). METHODS: A total of 170 ex vivo OCT images of the tumor, were acquired just after completion of thyroidectomy in 17 patients. The OCT images of each patient were separately evaluated by two blinded investigators, and the outcomes were compared with the histopathology reports. RESULTS: The sensitivity and specificity of mETE identification from the OCT images were 81.4% and 86.0%, respectively, for the first investigator, and 82.9% and 87.0%, respectively, for the second investigator. Substantial agreement between the investigators was verified by Cohen's κ (Cohen's κ = 0.772). CONCLUSION: In this preliminary study of a limited series of ex vivo thyroidectomy specimens, we verified the feasibility of OCT as a method of identifying mETE in patients with PTC.

Multimodal imaging using optical coherence tomography and endolaryngeal ultrasonography in a new rabbit VX2 laryngeal cancer model.

BACKGROUND AND OBJECTIVE: Optical coherence tomography (OCT) provides ultrahigh-resolution imaging of tissues within a depth of a few millimeters, whereas ultrasonography provides good imaging further below the surface. We aimed to develop a minimally invasive rabbit model of VX2 laryngeal cancer, suitable for these two imaging modalities through a transoral approach. We also sought to study the utility of combined OCT and endolaryngeal ultrasonography (EUS) for evaluation of early and advanced laryngeal cancer, using this model. MATERIALS AND METHODS: VX2 tumor suspension was inoculated into the vocal folds of ten rabbits by injection through the trans-thyrohyoid membrane. The tumor model was characterized by rigid laryngoscopy and the tumor generation rate was 80% (8/10). Correlation between frequency-domain OCT and high-frequency EUS were used to visualize laryngeal tumors in the area of protruding mass formation in four rabbits, one week after injection (group A) and the remaining four rabbits two weeks after injection (group B). RESULTS: A small submucosal tumor was observed with rigid laryngoscopy in group A, and pathologic evaluation showed that the tumor was close to the basement membrane of the vocal fold mucosa, but had not invaded. OCT confirmed that the lining of the mucosa and basement membrane of the vocal fold was not broken, but the mucosa had thinned at the most elevated ridge. However, these lesions were not detected by EUS, and the overall shape of the tumor could not be clearly identified by EUS. A large tumor filling the laryngeal lumen was observed with rigid laryngoscopy in group B, and nearly the entire vocal fold, including the paraglottic space, was found to be involved on pathologic analysis. Distinguishing between normal structures and tumor was difficult using OCT; however, EUS confirmed the overall shape, size, and extent of the tumor, and the paraglottic space and thyroid cartilage were shown to be intact. CONCLUSIONS: This study is the first experimental trial, assessing the value of multimodal imaging using OCT and EUS in a rabbit VX2 laryngeal tumor model. Combining OCT and EUS helped to identify changes in laryngeal mucous membranes, and could potentially be used to identify laryngeal tumors and predict how tumors progress. This combined modality could help in determining tumor extent, assisting in diagnosis, and establishing a treatment plan for laryngeal cancer.

In vivo real-time imaging of airway dynamics during bronchial challenge test.

BACKGROUND AND OBJECTIVE: Asthmatic patients exhibit airway hyper-responsiveness, which induces bronchoconstriction and results in a ventilation defect. The bronchial challenge test using methacholine is a useful way to measure airway hyper-responsiveness with airway constriction. Anatomical optical coherence tomography has been used to image airway hyper-responsiveness of medium sized bronchus with the aid of an endoscopic probe. Recently, a thoracic window was reported that allows direct visualization of terminal airway such as alveolus. A multi-scale integrated airway dynamics was assessed in this study. We imaged in vivo changes in the right intermedius bronchus and alveolar structure during the bronchial challenge test using two optical coherence tomography systems and correlated the changes with airway resistance. MATERIALS AND METHODS: Rabbits intubated with a non-cuffed endotracheal tube on a ventilator sequentially inhaled normal saline and methacholine (2 or 5 µg/ml). The airway resistance was measured by mechanical ventilation and airway structures were monitored by a commercial endoscopic optical coherence tomography system (1,310 nm) and a house-made table-top spectral-domain optical coherence tomography system (850 nm). RESULTS: We demonstrated an early decrease in the size of the right intermedius bronchus and alveoli in accordance with increased airway resistance after methacholine inhalation. OCT image after inhalation of 2 µg/ml methacholine showed some segmental narrowing of the right intermedius bronchus and the image after inhalation of 5 µg/ml methacholine showed even greater segmental narrowing. The cross-sectional areas were 7.2 ± 3.3 mm2 (normal saline), 3.7 ± 2.1 mm2 (2 µg/ml methacholine), and 2.4 ± 1.1 mm2 (5 µg/ml methacholine), respectively (P = 0.04). Most of the alveolar space was collapsed under elevated airway resistance with methacholine inhalation. The averaged areas per alveolus at the end of inspiration were 0.0244 ±0.0142 mm2 (normal saline), 0.0046 ±0.0026 mm2 (2 µg/ml methacholine), and 0.0048 ±0.0028 mm2 (5 µg/ml methacholine), respectively (P = 0.03). Methacholine induced a dose-dependent increase in airway resistance (1.1 ± 0.3 cm H2O sec/ml for 2 µg/ml methacholine, 1.5 ± 0.5 cm H2O sec/ml for 5 µg/ml methacholine) (P = 0.03). These results were obtained from normal rabbits during the bronchial challenge test with a non-cuffed endotracheal tube on a ventilator. With this setup increased airway resistance possibly resulted in larger leakage around the endotracheal tube, decreased inhaled volumes, and, in turn, alveolar collapse. CONCLUSION: We performed a feasibility study of in vivo visualization of real-time airway dynamics. To our best knowledge, this is the first report of real-time integrated airway dynamics including the right intermedius bronchus and alveoli during a bronchial challenge test. OCT showed bronchial constriction and alveolar collapse with a higher methacholine dose. OCT images correlated with the measured airway resistance. Therefore, OCT could be a potential diagnostic device for airway hyper-responsiveness and airway remodeling.

Multimodal real-time imaging with laser speckle contrast and fluorescent contrast.

INTRODUCTION: Laser speckle contrast imaging (LSCI) can achieve real-time 2D perfusion maps non-invasively. However, LSCI is still difficult to use in general clinical applications because of movement sensitivity and limitations in blood flow analysis. To overcome this, fluorescence imaging (FI) is combined with LSCI using a light source with a wavelength of 785 nm in near-infrared (NIR) region and validates to visualize real-time blood perfusion. MATERIALS AND METHODS: The system was performed using Intralipid and indocyanine green (ICG) in a flow phantom that has three tubes and controlled the flow rate in 0-150 µl/min range. First, real-time LSCI was monitored and measured the change in speckle contrast by reperfusion. Then, we visualized blood perfusion of a rabbit ear under the non-invasive condition by intravenous injection using a total of five different ICG concentration solutions from 128 µM to 3.22 mM. RESULTS: The combined system achieved the performance of processing laser speckle images at about 37-38 fps, and we simultaneously confirmed the fluorescence of ICG and changes in speckle contrast due to intralipid as a light scatterer. In addition, we obtained real-time contrast variation and fluorescent images occurring in rabbit's blood perfusion. CONCLUSIONS: The aim of this study is to provide a real-time diagnostic imaging system that can be used in general clinical applications. LSCI and FI are combined complementary for observing tissue perfusion using a single NIR light source. The combined system could achieve real-time visualization of blood perfusion non-invasively.

Time-Sequential Monitoring of the Early Mesothelial Reaction in the Pleura after Cryoinjury.

(1) Background: An early mesothelial reaction of the pleura, leading to fibrosis, has been reported in animals after chemical or heavy metal exposure. However, the visual monitoring of early time-sequential mesothelial reaction-associated cryoinjury has not been fully investigated. Therefore, this study aimed to evaluate and visualize the early mesothelial reactions seen following cryoinjury using rabbit pleura. (2) Methods: We monitored the early mesothelial reaction in rabbit pleurae after cryoinjury using optical coherence tomography (OCT), in real-time, which was then compared with pathological images. Due to the penetration limit of OCT, we made a thoracic window to image the parietal and visceral pleurae in vivo. We also used an innovative technique for capturing the microstructure in vivo, employing a computer-controlled intermittent iso-pressure breath hold to reduce respiratory motion, increasing the resolution of OCT. We organized three sample groups: the normal group, the sham group with just a thoracic window, and the experimental group with a thoracic window and cryotherapy. In the experimental group, localized cryoinjury was performed. The mesothelial cells at the level of pleura of the cryotherapy-injured site were visualized by OCT within the first 30 min and then again after 2 days at the same site. (3) Results: In the experimental group, focal thickening of the parietal pleura was observed at the site of cryoinjury using OCT after the first injury, and it was then confirmed pathologically as focal mesothelial cell proliferation. Two days after cryoinjury, diffuse mesothelial cell proliferation in the parietal pleura was noted on the reverse side around the cryoinjured site in the same rabbit. In the sham group, no pleural reaction was found. The OCT and pathological examinations revealed different patterns of mesothelial cell reactions between the parietal and visceral pleurae: the focal proliferation of mesothelial cells was found in the parietal pleura, while only a morphological change from flat cells to cuboidal cells and a thickened monolayer without proliferation of mesothelial cells were found in the visceral pleural. (4) Conclusions: An early mesothelial reaction occurs following cryoinjury to the parietal and visceral pleurae.

Detectable depth of unexposed parathyroid glands using near-infrared autofluorescence imaging in thyroid surgery.

Background: Near-infrared light can penetrate the fat or connective tissues overlying the parathyroid gland (PG), enabling early localization of the PG by near-infrared autofluorescence (NIRAF) imaging. However, the depth at which the PG can be detected has not been reported. In this study, we investigated the detectable depth of unexposed PGs using NIRAF during thyroidectomy. Materials and methods: Fifty-one unexposed PGs from 30 consecutive thyroidectomy patients, mapped by an experienced surgeon (K.D. Lee) with the use of NIRAF imaging, were included. For NIRAF detection of PGs, a lab-built camera imaging system was used. Detectable depths of the unexposed PGs were measured using a Vernier caliper. The NIRAF images were classified as faint or bright depending on whether a novice could successfully interpret the image as showing the PG. Data on variables that may affect detectable depth and NIRAF intensity were collected. Results: Detectable depth ranged between 0.35 and 3.05 mm, with a mean of 1.23 ± 0.73 mm. The average NIRAF intensity of unexposed PGs was 3.13 au. After dissection of the overlying tissue, the intensity of the exposed PG increased to 4.88 au (p < 0.001). No difference in NIRAF intensity between fat-covered (3.27 ± 0.90 au) and connective tissue-covered PGs (3.00 ± 1.23 au) was observed (p = 0.369). PGs covered by fat tissue (depth: 1.77 ± 0.67 mm) were found at deeper locations than those covered by connective tissue (depth: 0.70 ± 0.21 mm) (p < 0.001). The brightness of images of the faint group (2.14 ± 0.48 au) was on average 1.24 au lower than that of the bright group (3.38 ± 1.04 au) (p = 0.001). A novice successfully localized 80.4% of the unexposed PGs. Other variables did not significantly affect detectable depth. Conclusion: Unexposed PGs could be mapped using NIRAF imaging at a maximum depth of 3.05 mm and an average depth of 1.23 mm. A novice was able to localize the PGs before they were visible to the naked eye at a high rate. These results can be used as reference data for localization of unexposed PGs in thyroid surgery.

Effectiveness of Non-Contact Dietary Coaching in Adults with Diabetes or Prediabetes Using a Continuous Glucose Monitoring Device: A Randomized Controlled Trial.

We aimed to evaluate the effectiveness of dietary coaching and continuous glucose monitoring (CGM) in patients with diabetes or prediabetes to improve their behavioral skills and health outcomes. A randomized controlled study with pre- and post-testing was conducted. Data were collected between November 2020 and April 2021. Forty-five patients with diabetes or prediabetes who used a CGM device were enrolled and analyzed. Dietary education, individual coaching and group coaching were provided to participants in the experimental group for 4 weeks. After the intervention, the thigh circumference in men significantly differed between the two groups (z = -2.02, p = 0.044). For women, participants in the experimental group showed greater improvement in eating self-efficacy compared with those in the control group (z = -2.66, p = 0.008). Insomnia was negatively related to the change in eating self-efficacy (r = -0.35, p = 0.018) and increase in thigh circumference (r = -0.35, p = 0.017). Even if used within a short intervention period, non-contact dietary coaching programs can help enhance behavioral skills, such as eating self-efficacy and health outcomes, such as thigh circumference. Moreover, the changed variables can indirectly improve other health outcomes in patients with diabetes or prediabetes.

Near-infrared Transillumination and Photodynamic Therapy Using Hypericin in Animal Laryngeal Tumors.

BACKGROUND: We aimed to validate a pilot study of photodiagnosis using near infrared (NIR) transillumination and assess the clinical efficacy of hypericin-mediated photodynamic therapy (HYP-PDT) in a rabbit laryngeal cancer model in order to develop a novel therapeutic modality with complete remission and preservation of the functional organ. METHODS: (1) In vitro study: VX tumor cells were subcultured and subjected to HYP-PDT. (2) In vivo study: A laryngeal cancer model was developed in which 12 rabbits were inoculated with a VX tumor suspension in the submucosal area of the left vocal fold using a transoral approach. All rabbits underwent NIR transillumination using light with a wavelength of 780 nm. The survival periods of the three treatment groups (6 rabbits in Group A: HYP-PDT, 3 each in Groups B and C: laser irradiation or HYP administration only) were analyzed. RESULTS: The higher the HYP concentration, the lower the VX cell viability in response to HYP-PDT using 590 nm LED. Following HYP-PDT, small tumors in Group A-1 rabbits healed completely and the animals demonstrated a long survival period, and larger tumors in Group A-2 healed partially with a survival period that extended over 3 weeks after inoculation. The survival of Groups B and C were not different over the first 3 weeks of the study, and were shorter than in Group A. CONCLUSION: We found HYP-PDT could be a curative therapy for early-stage cancers that may also preserve organ function, and may inhibit tumor progression and metastasis during advanced stages of laryngeal cancer.

Application of Polarization Sensitive-Optical Coherence Tomography to the Assessment of Phase Retardation in Subpleural Cancer in Rabbits.

BACKGROUND: Polarization sensitive-optical coherence tomography (PS-OCT) provides the unique advantage of being able to measure the optical characteristics of tissues by using polarized light. Although the well-organized fibers of healthy muscle can change the polarization states of passing light, damaged tissue has different behaviors. There are studies on optical imaging methods applied to the respiratory organs; however, they are restricted to structural imaging. In particular, the intercostal muscle situated under the pleura is very challenging to visualize due to the difficulty of access. METHOD: In this study, PS-OCT was used to identify subpleural cancer in male New Zealand white rabbits (3.2-3.4 kg) and to assess the phase retardation changes in normal and cancerous chest walls. VX2 cell suspension was injected between the intercostal muscle and parietal pleura and a tented area was observed by thoracic scope. A group of rabbits (n = 3) were sacrificed at day 7 after injection and another group (n = 3) at day 14. RESULTS: In the PS-OCT images, pleura thickness changes and muscle damage were criteria to understand the stages of the disease. The results of image and phase retardation analysis matched well with the pathologic examinations. CONCLUSION: We were able to visualize and analyze subpleural cancer by PS-OCT, which provided structural and functional information. The measured phase retardation could help to identify the margin of the tumor. For further studies, various approaches into other diseases using polarization light are expected to have positive results.

Investigation of the Clinical Potential of Polarization-Sensitive Optical Coherence Tomography in a Laryngeal Tumor Model.

BACKGROUND: The vocal cord tissue consists of three anatomical layers from the surface to deep inside: the epithelium that contains almost no collagen, the lamina propria that is composed of abundant collagen, and the vocalis muscle layer. It is clinically important to visualize the tissue microstructure using a non-invasive method, especially in the case of vocal cord nodules or cancer, since histological changes in each layer of the vocal cord cause changes in the voice. Polarization-sensitive optical coherence tomography (PS-OCT) enables phase retardation measurement to evaluate birefringence of tissue with varied organization of collagen fibers in different tissue layers. Therefore, PS-OCT can visualize structural changes between normal and abnormal vocal cord tissue. METHOD: A rabbit laryngeal tumor model with different stages of tumor progression was investigated ex-vivo by PS-OCT. A phase retardation slope-based analysis, which quantifies the birefringence in different layers, was conducted to distinguish the epithelium, lamina propria, and muscle layers. RESULTS: The PS-OCT images showed a gradual decrease in birefringence from normal tissue to advanced tumor tissue. The quantitative analysis provided a more detailed comparison among different stages of the rabbit laryngeal tumor model, which was validated by the corresponding histological findings. CONCLUSION: Differences in tissue birefringence was evaluated by PS-OCT phase retardation measurement. It is also possible to indirectly infer the dysplastic changes based on the mucosal and submucosal alterations.

Near-Infrared Autofluorescence Imaging May Reduce Temporary Hypoparathyroidism in Patients Undergoing Total Thyroidectomy and Central Neck Dissection.

Background: Near-infrared autofluorescence (NIRAF) imaging is known to reduce the incidence of post-thyroidectomy hypocalcemia. However, there are no studies on how much NIRAF imaging affects the serum parathyroid hormone (PTH) level after surgery. We investigated the changes of the serum PTH level and ionized calcium (iCa.) in patients undergoing total thyroidectomy with central neck dissection (CND). Materials and Methods: This retrospective study with historical control enrolled 542 patients who underwent total thyroidectomy with CND. Patients were divided into two groups: the NIRAF group (261 patients) and the control group (281 patients). PTH and iCa. levels were measured at the hospital stay, 1, 3, and 6 months after surgery. In addition, the number of identified parathyroid glands (PGs), autotransplanted PGs, and the inadvertent resection rate of PGs was evaluated. Results: The incidence of postoperative hypoparathyroidism (PTH <15 pg/mL) was significantly lower in the NIRAF group during the hospitalization (88 patients: 33.7% vs. 131 patients: 46.6%; p = 0.002) and at 1 month postoperatively (23 patients: 8.8% vs. 53 patients: 18.9%; p = 0.001). There was no difference in the permanent hypoparathyroidism rate (6 months after surgery) between the NIRAF group and the control group (4.2% vs. 4.6%; p = 0.816). There was no difference in the incidence of hypocalcemia (iCa. <1.09 mmol/L) (during hospitalization: 6.5% vs. 10.0%; 1 month: 2.3% vs. 2.5%; 3 months: 0.8% vs. 0.7%; 6 months after surgery: 1.1% vs. 1.1%) between the two groups. The number of inadvertently resected PGs was significantly lower in the NIRAF group (18:6.9% vs. 36:12.8%; p = 0.021). Conclusions: These results suggest that NIRAF imaging may reduce temporary hypoparathyroidism and the risk of inadvertent resection of PGs in patients undergoing total thyroidectomy with CND.

Combined multimodal optical imaging and targeted gene silencing using stimuli-transforming nanotheragnostics.

Combined diagnosis and therapy for cancer has been of great interest in medicine. Small interference RNA (siRNA)-encapsulating polyplexes were covalently coated with small gold nanoparticles (Au NPs) via acid-cleavable linkages in order to explore the possibility of achieving combined stimuli-responsive multimodal optical imaging and stimuli-enhanced gene silencing. In a mildly acidic tumor environment, Au NPs are dissociated from the siRNA-carrying polyplexes, generating various optical signal changes such as diminished scattering intensity, increased variance of Doppler frequency, and blue-shifted UV absorbance (stimuli-responsive imaging). Simultaneously, Au NP dissociation exposes the siRNA-carrying polyplex with elevated surface charge and results in enhanced cellular uptake and transfection (stimuli-enhanced therapy). In this study, the feasibility of achieving combined diagnosis and therapy for cancer (theragnostics) is demonstrated by (1) microscopic and spectrophotometric confirmation of acid-transformation of the nanoparticles, (2) reduced scattering intensity and increased variance of Doppler frequency in an acidic pH upon the nanoparticle's transformation, and (3) simultaneous optical signal changes and gene silencing in vitro under a tumor pH-mimicking condition. This novel type of stimuli-responsive nanotheragnostics will provide a new paradigm for pinpointed, multimodal, and combined imaging and therapy for cancer.

Ability of optical coherence tomography to detect caries beneath commonly used dental sealants.

BACKGROUND AND OBJECTIVE: The onset and progression of early tooth decay is often preventable with dental sealants. However, occasionally decay progresses underneath the sealant. Current technology does not permit monitoring of potential lesion progression or arrest. Dental sealants themselves mask the visual cues that identify early tooth decay, and radiographs are not sufficiently sensitive. Therefore, clinicians can be reluctant to use dental sealant. The objective of this ex vivo study was to evaluate the ability of dentists to detect decay beneath commonly used dental sealants using optical coherence tomography (OCT) imaging. STUDY DESIGNS/MATERIALS/METHODS: Forty extracted teeth were divided into equal groups of carious and non-carious teeth, as determined by visual inspection. After radiographs and OCT imaging, teeth were randomly assigned for sealant placement with one of four commonly purchased dental sealants: Clinpro™, Fuji Triage™, Embrace Wet Bond™, and Delton™.Following sealant placement, teeth were radiographed, imaged with OCT, sectioned, examined histologically, and scored as healthy/not healthy. OCT and radiographic images were scored separately. The gold standard was histopathological diagnosis from the serial sections.Cohen's kappa, sensitivity, negative predictive value, and positive predictive value were computed for all measures. RESULTS: After 90 minutes training, pre-standardized dentists were able to detect tooth decay more accurately using OCT than with visual or radiographic examination. Detection using OCT was somewhat better prior to sealant placement than afterwards. This effect varied in size depending on the type of sealant used. Radiographic diagnosis was also less accurate after sealant placement. Of the four dental sealants, Delton provided excellent positive predictive value and the best post-sealant negative predictive values. CONCLUSION: In this ex vivo study, dentists were able to detect tooth decay beneath four commonly used dental sealants based on OCT images. Clinical investigations are now underway to determine the usefulness of this approach in vivo.

Phase-sensitive fluorescence detector for parathyroid glands during thyroidectomy: A preliminary report.

Despite advances in medical technology, the parathyroid glands are still damaged during thyroid surgery. Our previous studies exploring methods for locating the parathyroid glands using autofluorescence have limitations, such as turning off the surgical light or requiring additional matching between the autofluorescence image and real-surgical field-of-view. We developed a probe-type parathyroid autofluorescence detector using a phase-sensitive process and optical filtering to overcome these limitations. A preliminary clinical trial was performed on eight parathyroid glands in four patients. The normalized mean signal of the normal parathyroid glands was 332% stronger than that of the thyroid, and 384%, 459% and 286% stronger than the signal of the muscle, trachea and fat, respectively. Additionally, the device also detected fluorescence from indocyanine green.

Multimodality bronchoscopic [corrected] imaging of tracheopathica osteochondroplastica.

Results of a commercial optical coherence tomography system used as part of a multimodality diagnostic bronchoscopy platform are presented for a 61-year-old patient with central airway obstruction from tracheopathica osteochondroplastica. Comparison to results of white-light bronchoscopy, histology, and endobronchial ultrasound examination are accompanied by a discussion of resolution, penetration depth, contrast, and field of view of these imaging modalities. White-light bronchoscopy revealed irregularly shaped, firm submucosal nodules along cartilaginous structures of the anterior and lateral walls of the trachea, sparing the muscular posterior membrane. Endobronchial ultrasound showed a hyperechoic density of 0.4 cm thickness. optical coherence tomography (OCT) was performed using a commercially available, compact time-domain OCT system (Niris System, Imalux Corp., Cleveland, Ohio) with a magnetically actuating probe (two-dimensional, front imaging, and inside actuation). Images showed epithelium, upper submucosa, and osseous submucosal nodule layers corresponding with histopathology. To our knowledge, this is the first time these commercially available systems are used as part of a multimodality bronchoscopy platform to study diagnostic imaging of a benign disease causing central airway obstruction. Further studies are needed to optimize these systems for pulmonary applications and to determine how new-generation imaging modalities will be integrated into a multimodality bronchoscopy platform.

Design and implementation of fiber-based multiphoton endoscopy with microelectromechanical systems scanning.

A multiphoton endoscopy system has been developed using a two-axis microelectromechanical systems (MEMS) mirror and double-cladding photonic crystal fiber (DCPCF). The MEMS mirror has a 2-mm-diam, 20-deg optical scanning angle, and 1.26-kHz and 780-Hz resonance frequencies on the x and y axes. The maximum number of resolvable focal spots of the MEMS scanner is 720 x 720 on the x and y axes, which indicates that the MEMS scanner can potentially support high-resolution multiphoton imaging. The DCPCF is compared with standard single-mode fiber and hollow-core photonic bandgap fiber on the basis of dispersion, attenuation, and coupling efficiency properties. The DCPCF has high collection efficiency, and its dispersion can be compensated by grating pairs. Three configurations of probe design are investigated, and their imaging quality and field of view are compared. A two-lens configuration with a collimation and a focusing lens provides the optimum imaging performance and packaging flexibility. The endoscope is applied to image fluorescent microspheres and bovine knee joint cartilage.

Enhanced detection of early-stage oral cancer in vivo by optical coherence tomography using multimodal delivery of gold nanoparticles.

Contrast in optical coherence tomography (OCT) images can be enhanced by utilizing surface plasmon resonant gold nanoparticles. To improve the poor in vivo transport of gold nanoparticles through biological barriers, an efficient delivery strategy is needed. In this study, the improved penetration and distribution of gold nanoparticles were achieved by microneedle and ultrasound, respectively, and it was demonstrated that this multimodal delivery of antibody-conjugated PEGylated gold nanoparticles enhanced the contrast in in vivo OCT images of oral dysplasia in a hamster model.

Optimization for Axial Resolution, Depth Range, and Sensitivity of Spectral Domain Optical Coherence Tomography at 1.3 µm.

We have developed high-speed and high-resolution spectral domain optical coherence tomography at 1.3 µm using an InGaAs line-scan camera and a broadband light source with the bandwidth of 170 nm that produces a theoretical axial resolution of 4.4 µm in air. We compared axial resolutions from point spread functions (PSFs) and depth ranges while changing the full spectral bandwidth detected by the camera and describing the optimization process for the axial resolution, the depth range, and the sensitivity for SD-OCT system. We found that SD-OCT at 1.3 µm cannot satisfy the conditions both below the axial resolution of 5 µm and above the depth range of 2 mm because of the restricted pixel number of the line-scan camera. To scan a large depth range, the axial resolution has to be sacrificed. In addition, the sensitivity rolls off slowly as a function of the depth if a large depth range is scanned. On the other hand, if the axial resolution needs to be close to the theoretical one, the depth range becomes limited and the sensitivity decays quickly. Since we have to maintain a reasonable depth range of 2.0 mm, we chose the spectrum full bandwidth of 214 nm captured by the detector to balance the axial resolution of 8.2 µm. In this setting, the sensitivity of our OCT system was measured at 107.1 dB. Theoretical and experimental results are compared and presented in this paper.

Video-assisted parathyroid gland mapping with autofocusing.

Preservation of the parathyroid gland (PTG) in neck endocrine surgery is important for regulating the amount of calcium in the blood and within the bones. Localization of the PTG has been attempted using various methods such as ultrasound, sestamibi, computerized tomography, magnetic resonance imaging and indocyanine green fluorescence imaging. These methods cannot be used during surgery, have high sensitivity or have PTG specificity. However, autofluorescence technique has shown high sensitivity and does not require exogenous contrast. In this study, a new optical system was designed and developed into a clinical system. The system enabled easier and faster focusing on the surgical area and high-resolution video imaging while maintaining a clear image. The system was located above the head of the surgeon. The surgeon was able to see the real-time autofluorescent image on the monitor next to the operating table at any time to locate the PTG. The PTG buried in the adipose tissue and connective tissue was located easily and accurately. The clinical trial conducted in this study consisted of 56 parathyroid cases in 26 patients. For the statistical results, the sensitivity and accuracy in this redesigned autofluorescent imaging system were 98.1% and 96.4%, respectively.