Computational imaging with spectral coding increases the spatial resolution of fiber optic bundles.

Fiber optic bundles are used in narrow-diameter medical and industrial instruments for acquiring images from confined locations. Images transmitted through these bundles contain only one pixel of information per fiber core and fail to capture information from the cladding region between cores. Both factors limit the spatial resolution attainable with fiber bundles. We show here that computational imaging (CI) can be combined with spectral coding to overcome these two fundamental limitations and improve spatial resolution in fiber bundle imaging. By acquiring multiple images of a scene with a high-resolution mask pattern imposed, up to 17 pixels of information can be recovered from each fiber core. A dispersive element at the distal end of the bundle imparts a wavelength-dependent lateral shift on light from the object. This enables light that would otherwise be lost at the inter-fiber cladding to be transmitted through adjacent fiber cores. We experimentally demonstrate this approach using synthetic and real objects. Using CI with spectral coding, object features 5× smaller than individual fiber cores were resolved, whereas conventional imaging could only resolve features at least 1.5× larger than each core. In summary, CI combined with spectral coding provides an approach for overcoming the two fundamental limitations of fiber optic bundle imaging.

Short-Wave Infrared Emitting Nanocomposites for Fluorescence-Guided Surgery.

Fluorescence-guided surgery (FGS) is an emerging technique for tissue visualization during surgical procedures. Structures of interest are labeled with exogenous probes whose fluorescent emissions are acquired and viewed in real-time with optical imaging systems. This study investigated rare-earth-doped albumin-encapsulated nanocomposites (REANCs) as short-wave infrared emitting contrast agents for FGS. Experiments were conducted using an animal model of 4T1 breast cancer. The signal-to-background ratio (SBR) obtained with REANCs was compared to values obtained using indocyanine green (ICG), a near-infrared dye used in clinical practice. Prior to resection, the SBR for tumors following intratumoral administration of REANCs was significantly higher than for tumors injected with ICG. Following FGS, evaluation of fluorescence intensity levels in excised tumors and at the surgical bed demonstrated higher contrast between tissues at these sites with REANC contrast than ICG. REANCs also demonstrated excellent photostability over 2 hours of continuous illumination, as well as the ability to perform FGS under ambient lighting, establishing these nanocomposites as a promising contrast agent for FGS applications.

Shortwave infrared emitting multicolored nanoprobes for biomarker-specific cancer imaging in vivo.

BACKGROUND: The ability to detect tumor-specific biomarkers in real-time using optical imaging plays a critical role in preclinical studies aimed at evaluating drug safety and treatment response. In this study, we engineered an imaging platform capable of targeting different tumor biomarkers using a multi-colored library of nanoprobes. These probes contain rare-earth elements that emit light in the short-wave infrared (SWIR) wavelength region (900-1700 nm), which exhibits reduced absorption and scattering compared to visible and NIR, and are rendered biocompatible by encapsulation in human serum albumin. The spectrally distinct emissions of the holmium (Ho), erbium (Er), and thulium (Tm) cations that constitute the cores of these nanoprobes make them attractive candidates for optical molecular imaging of multiple disease biomarkers. METHODS: SWIR-emitting rare-earth-doped albumin nanocomposites (ReANCs) were synthesized using controlled coacervation, with visible light-emitting fluorophores additionally incorporated during the crosslinking phase for validation purposes. Specifically, HoANCs, ErANCs, and TmANCs were co-labeled with rhodamine-B, FITC, and Alexa Fluor 647 dyes respectively. These Rh-HoANCs, FITC-ErANCs, and 647-TmANCs were further conjugated with the targeting ligands daidzein, AMD3100, and folic acid respectively. Binding specificities of each nanoprobe to distinct cellular subsets were established by in vitro uptake studies. Quantitative whole-body SWIR imaging of subcutaneous tumor bearing mice was used to validate the in vivo targeting ability of these nanoprobes. RESULTS: Each of the three ligand-functionalized nanoprobes showed significantly higher uptake in the targeted cell line compared to untargeted probes. Increased accumulation of tumor-specific nanoprobes was also measured relative to untargeted probes in subcutaneous tumor models of breast (4175 and MCF-7) and ovarian cancer (SKOV3). Preferential accumulation of tumor-specific nanoprobes was also observed in tumors overexpressing targeted biomarkers in mice bearing molecularly-distinct bilateral subcutaneous tumors, as evidenced by significantly higher signal intensities on SWIR imaging. CONCLUSIONS: The results from this study show that tumors can be detected in vivo using a set of targeted multispectral SWIR-emitting nanoprobes. Significantly, these nanoprobes enabled imaging of biomarkers in mice bearing bilateral tumors with distinct molecular phenotypes. The findings from this study provide a foundation for optical molecular imaging of heterogeneous tumors and for studying the response of these complex lesions to targeted therapy.

An Experimental Review of Optical Coherence Tomography Systems for Noninvasive Assessment of Hard Dental Tissues.

Optical coherence tomography (OCT) is a noninvasive, high-resolution, cross-sectional imaging technique. To date, OCT has been demonstrated in several areas of dentistry, primarily using wavelengths around 1,300 nm, low numerical aperture (NA) imaging lenses, and detectors insensitive to the polarization of light. The objective of this study is to compare the performance of three commercially available OCT systems operating with alternative wavelengths, imaging lenses, and detectors for OCT imaging of dental enamel. Spectral-domain (SD) OCT systems with (i) 840 nm (Lumedica, OQ LabScope 1.0), (ii) 1,300 nm (Thorlabs, Tel320) center wavelengths, and (iii) a swept-source (SS) OCT system (Thorlabs OCS1300SS) centered at 1,325 nm with optional polarization-sensitive detection were used. Low NA (0.04) and high NA (0.15) imaging lenses were used with system (iii). Healthy in vivo and in vitrohuman enamel and eroded in vitro bovine enamel specimens were imaged. The Tel320 system achieved greater imaging depth than the OQ LabScope 1.0, on average imaging 2.6 times deeper into the tooth (n = 10). The low NA lens provided a larger field of view and depth of focus, while the high NA lens provided higher lateral resolution and greater contrast. Polarization-sensitive imaging eliminated birefringent banding artifacts that can appear in conventional OCT scans. In summary, this study illustrates the performance of three commercially available OCT systems, objective lenses, and imaging modes and how these can affect imaging depth, resolution, field of view, and contrast in enamel. Users investigating OCT for dental applications should consider these factors when selecting an OCT system for clinical or basic science studies.

Computational endoscopy-a framework for improving spatial resolution in fiber bundle imaging.

This Letter presents a framework for computational imaging (CI) in fiber-bundle-based endoscopy systems. Multiple observations are acquired of objects spatially modulated with different random binary masks. Sparse-recovery algorithms then reconstruct images with more resolved pixels than individual fibers in the bundle. Object details lying within the diameter of single fibers are resolved, allowing images with 41,663 resolvable points to be generated through a bundle with 2,420 fibers. Computational fiber bundle imaging of micro- and macro-scale objects is demonstrated using fluorescent standards and biological tissues, including in vivo imaging of a human fingertip. In each case, CI recovers details that conventional endoscopy does not provide.

Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial.

BACKGROUND & AIMS: Esophageal squamous cell neoplasia has a high mortality rate as a result of late detection. In high-risk regions such as China, screening is performed by Lugol's chromoendoscopy (LCE). LCE has low specificity, resulting in unnecessary tissue biopsy with a subsequent increase in procedure cost and risk. The purpose of this study was to evaluate the accuracy of a novel, low-cost, high-resolution microendoscope (HRME) as an adjunct to LCE. METHODS: In this prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and 2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed white-light endoscopy followed by LCE and HRME. All optical images were compared with the gold standard of histopathology. RESULTS: By using a per-biopsy analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832), specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45% (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16), specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%, 100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136 biopsies (60%; 95% confidence interval, 53%-66%) could have been spared, and 55 patients (48%; 95% confidence interval, 38%-57%) could have been spared any biopsy. CONCLUSIONS: In this trial, HRME improved the accuracy of LCE for esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost-effective optical biopsy adjunct to LCE, potentially reducing unnecessary biopsies and facilitating real-time decision making in globally underserved regions. ClinicalTrials.gov, NCT 01384708.

Computational imaging with a highly parallel image-plane-coded architecture: challenges and solutions.

This paper investigates a highly parallel extension of the single-pixel camera based on a focal plane array. It discusses the practical challenges that arise when implementing such an architecture and demonstrates that system-specific optical effects must be measured and integrated within the system model for accurate image reconstruction. Three different projection lenses were used to evaluate the ability of the system to accommodate varying degrees of optical imperfection. Reconstruction of binary and grayscale objects using system-specific models and Nesterov's proximal gradient method produced images with higher spatial resolution and lower reconstruction error than using either bicubic interpolation or a theoretical system model that assumes ideal optical behavior. The high-quality images produced using relatively few observations suggest that higher throughput imaging may be achieved with such architectures than with conventional single-pixel cameras. The optical design considerations and quantitative performance metrics proposed here may lead to improved image reconstruction for similar highly parallel systems.

Quantitative analysis of high-resolution microendoscopic images for diagnosis of neoplasia in patients with Barrett's esophagus.

BACKGROUND AND AIMS: Previous studies show that microendoscopic images can be interpreted visually to identify the presence of neoplasia in patients with Barrett's esophagus (BE), but this approach is subjective and requires clinical expertise. This study describes an approach for quantitative image analysis of microendoscopic images to identify neoplastic lesions in patients with BE. METHODS: Images were acquired from 230 sites from 58 patients by using a fiberoptic high-resolution microendoscope during standard endoscopic procedures. Images were analyzed by a fully automated image processing algorithm, which automatically selected a region of interest and calculated quantitative image features. Image features were used to develop an algorithm to identify the presence of neoplasia; results were compared with a histopathology diagnosis. RESULTS: A sequential classification algorithm that used image features related to glandular and cellular morphology resulted in a sensitivity of 84% and a specificity of 85%. Applying the algorithm to an independent validation set resulted in a sensitivity of 88% and a specificity of 85%. CONCLUSIONS: This pilot study demonstrates that automated analysis of microendoscopic images can provide an objective, quantitative framework to assist clinicians in evaluating esophageal lesions from patients with BE. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01384227 and NCT02018367.).

A Phase I, Open-Label, Single-Dose Safety, Pharmacokinetic, and Tolerability Study of the Sumatriptan Iontophoretic Transdermal System in Adolescent Migraine Patients.

OBJECTIVE: To evaluate the safety, tolerability, and pharmacokinetics of sumatriptan delivered by the iontophoretic transdermal system (TDS) in adolescent patients. BACKGROUND: Since nausea can be a prominent and early symptom of migraine, nonoral treatment options are often required. Sumatriptan iontophoretic TDS is approved for the acute treatment of migraine in adults. The present study evaluates the pharmacokinetics of sumatriptan administered via the iontophoretic TDS in adolescents, contrasting the findings with historical data from adults. DESIGN: Patients aged 12-17 years (inclusive) with acute migraine were treated with sumatriptan iontophoretic TDS for 4 hours. Blood samples for pharmacokinetic profiling of sumatriptan were obtained prior to dosing and at predetermined time points covering the 12 hours postonset of treatment. Key pharmacokinetic endpoints included Cmax (peak plasma drug concentration), tmax (time to Cmax ), AUC0-∞ (area under the plasma concentration-time curve from time 0 to infinity), and t½ (terminal elimination half-life). Safety was evaluated by monitoring of adverse events in addition to laboratory and clinical assessments. RESULTS: The sample consisted of 37 patients, and 36 were included in the PK evaluable population. Cmax , tmax , AUC0-∞ , and t½ values were all similar between male and female patients and between younger (12-14 years) and older (15-17 years) adolescents. When compared with historical adult data, adolescent patients demonstrated similar systemic exposures to those observed in adults (mean Cmax 20.20 (±6.43) ng/mL in adolescents vs 21.89 (±6.15) ng/mL in adults; mean AUC0-∞ 98.1 (±28.1) ng·h/mL in adolescents vs 109.7 (±26.1) ng·h/mL in adults). All adverse events were mild or moderate, with application-site paresthesia being the most common (32%). No clinically relevant changes in laboratory values, vital signs, or electrocardiogram findings were observed. CONCLUSIONS: The iontophoretic TDS produced mean systemic exposures to sumatriptan in younger and older adolescents, in line with what was seen in adult subjects. It was generally well tolerated.

Quantitative analysis of high-resolution microendoscopic images for diagnosis of esophageal squamous cell carcinoma.

BACKGROUND & AIMS: High-resolution microendoscopy is an optical imaging technique with the potential to improve the accuracy of endoscopic screening for esophageal squamous neoplasia. Although these microscopic images can be interpreted readily by trained personnel, quantitative image analysis software could facilitate the use of this technology in low-resource settings. In this study, we developed and evaluated quantitative image analysis criteria for the evaluation of neoplastic and non-neoplastic squamous esophageal mucosa. METHODS: We performed an image analysis of 177 patients undergoing standard upper endoscopy for screening or surveillance of esophageal squamous neoplasia, using high-resolution microendoscopy, at 2 hospitals in China and at 1 hospital in the United States from May 2010 to October 2012. Biopsy specimens were collected from imaged sites (n = 375), and a consensus diagnosis was provided by 2 expert gastrointestinal pathologists and used as the standard. RESULTS: Quantitative information from the high-resolution images was used to develop an algorithm to identify high-grade squamous dysplasia or invasive squamous cell cancer, based on histopathology findings. Optimal performance was obtained using the mean nuclear area as the basis for classification, resulting in sensitivities and specificities of 93% and 92% in the training set, 87% and 97% in the test set, and 84% and 95% in an independent validation set, respectively. CONCLUSIONS: High-resolution microendoscopy with quantitative image analysis can aid in the identification of esophageal squamous neoplasia. Use of software-based image guides may overcome issues of training and expertise in low-resource settings, allowing for widespread use of these optical biopsy technologies.

CXCR-4 Targeted, Short Wave Infrared (SWIR) Emitting Nanoprobes for Enhanced Deep Tissue Imaging and Micrometastatic Cancer Lesion Detection.

Realizing the promise of precision medicine in cancer therapy depends on identifying and tracking cancerous growths to maximize treatment options and improve patient outcomes. This goal of early detection remains unfulfilled by current clinical imaging techniques that fail to detect lesions due to their small size and suborgan localization. With proper probes, optical imaging techniques can overcome this by identifying the molecular phenotype of tumors at both macroscopic and microscopic scales. In this study, the first use of nanophotonic short wave infrared technology is proposed to molecularly phenotype small lesions for more sensitive detection. Here, human serum albumin encapsulated rare-earth nanoparticles (ReANCs) with ligands for targeted lesion imaging are designed. AMD3100, an antagonist to CXCR4 (a classic marker of cancer metastasis) is adsorbed onto ReANCs to form functionalized ReANCs (fReANCs). fReANCs are able to preferentially accumulate in receptor positive lesions when injected intraperitoneally in a subcutaneous tumor model. fReANCs can also target subtissue microlesions at a maximum depth of 10.5 mm in a lung metastatic model of breast cancer. Internal lesions identified with fReANCs are 2.25 times smaller than those detected with ReANCs. Thus, an integrated nanoprobe detection platform is presented, which allows target-specific identification of subtissue cancerous lesions.

Sumatriptan Iontophoretic Transdermal System Reduces Treatment-Emergent Nausea and Is Effective in Patients With and Without Nausea at Baseline - Results From a Randomized Controlled Trial.

OBJECTIVES: To test the hypothesis that sumatriptan iontophoretic transdermal system (TDS) is associated with lower rates of treatment-emergent nausea (TEN) relative to placebo, as well as to compare the efficacy of sumatriptan TDS in migraineurs with or without nausea at baseline. METHODS: Participants of a double-blind, randomized, parallel-group, single-attack, placebo-controlled study conducted at 38 sites in the United States were analyzed. Participants who treated their migraine attacks while nausea-free were identified. The primary endpoint was TEN over 24 hours post-treatment contrasting both treatment groups and it was assessed by regression analyses using generalized estimating equations. Secondary endpoint was headache response as a function of presence of nausea, assessed by generalized linear model. RESULTS: A total of 130 participants free of nausea at baseline were treated with sumatriptan TDS, while 109 participants free of nausea at baseline were treated with placebo TDS. The occurrence of TEN over 24 hours post-treatment was significantly lower with the sumatriptan TDS than with placebo (P = .0011). These differences were statistically significant at 1 hour (13.8% vs 9.2%, P < .01), 2 hours (13.8% vs 4.6% P < .001) and 3 hours (13.8% vs 8.5% P < .01). The efficacy of sumatriptan TDS was similar regardless of the presence or absence of nausea at baseline for all clinical parameters. CONCLUSION: Sumatriptan TDS is not associated with the emergence of nausea in migraineurs without nausea. It is equally effective in participants with or without nausea at the time of treatment.

Sumatriptan transdermal system can be correctly assembled and applied during migraine attacks.

OBJECTIVE: The objective of this study was to validate the ease of assembly and application of the sumatriptan iontophoretic transdermal system (sumatriptan TDS, Zecuity® , NuPathe, Inc., Malvern, PA, USA) during a migraine attack. BACKGROUND: Iontophoresis is a noninvasive drug delivery method using low electrical current to move solubilized drugs across the skin to the underlying tissue. With sumatriptan TDS, a pre-programmed dose of sumatriptan is automatically delivered via a transdermal patch, allowing therapeutic drug levels to be reached without mechanical penetration or disruption of the skin. Because migraine attacks can be disabling, with many patients unable to perform their usual activities, it is important for prescribers and their patients to be confident that they will be able to assemble and apply sumatriptan TDS in the middle of an attack. A human factor use study was conducted to evaluate the ease of assembly and application of the sumatriptan TDS among migraineurs and healthcare professionals (HCPs) who are likely to instruct patients on how to use the patch. METHODS: This was a single-center, open-label study assessing a single use of sumatriptan TDS in adult migraineurs and HCPs. Subjects were divided into 3 groups: migraineurs trained to use sumatriptan TDS, migraineurs not trained to use sumatriptan TDS, and HCPs not trained to use sumatriptan TDS. Sixteen subjects (trained migraineurs and untrained HCPs) participated in a preliminary usability test, and 48 subjects (16 representing each of the 3 groups) participated in a formal final test. Subjects were 20-64 years old, inclusive, and 83% female. They rated usability on a scale of 1-7, with 1 being difficult and 7 being easy. RESULTS: Preliminary testing.-Of the 16 sumatriptan TDS patches assembled and applied, 100% (16/16) were assembled and applied successfully. The mean score for ease of assembly was 6.3, and the mean score for ease of application was 6.8 out of 7, with 1 being difficult and 7 being easy. No modifications were made to patient instructions for use, patient labeling, or patient video for the final phase of testing. Final testing.-Of the 48 sumatriptan TDS patches assembled and applied during final testing, 100% (48/48) were assembled and applied successfully, with no user errors, one close call, and no operational difficulties observed. Across all 3 groups, the mean score for ease of assembly was 6.1, and the mean score for ease of application was 6.8 out of 7, with 1 being difficult and 7 being easy. For migraineurs who were trained and subsequently returned to the testing facility for evaluation of usability while in distress of a mild to severe migraine attack, the number of days between training and testing ranged from 0 to 20, with a mean of 3.6. Among untrained and trained migraineurs, 3.1% had a mild attack, 68.8% had a moderate attack, and 28.1% had a severe attack. CONCLUSIONS: The results of this study indicate that sumatriptan TDS can be assembled and applied successfully during a mild to severe migraine attack. Across all subject groups in both the preliminary and final testing, including trained and untrained migraineurs in distress of a migraine attack (96.9% moderate to severe) and untrained HCPs not experiencing a migraine attack, patch assembly and application was 100% successful. In the final test, subjects rated sumatriptan TDS very high for ease of assembly (6.1 out of 7, with 7 being easy) and ease of use (6.8 out of 7, with 7 being easy). These results indicate that patients and HCPs can be confident that patients can readily assemble and use sumatriptan TDS during a migraine attack. SHORT SUMMARY: A human factor use study evaluating ease of assembly and application of the sumatriptan transdermal system (TDS) among 64 migraineurs and HCPs found that patch assembly and application was 100% successful. Sumatriptan TDS scored 6.1 out of 7 for ease of assembly and 6.8 out of 7 for ease of use (with 7 being easy). Patients and HCPs can be confident that patients can assemble and use sumatriptan TDS during a migraine attack.

Early Detection of Myeloid-Derived Suppressor Cells in the Lung Pre-Metastatic Niche by Shortwave Infrared Nanoprobes.

Metastatic breast cancer remains a significant source of mortality amongst breast cancer patients and is generally considered incurable in part due to the difficulty in detection of early micro-metastases. The pre-metastatic niche (PMN) is a tissue microenvironment that has undergone changes to support the colonization and growth of circulating tumor cells, a key component of which is the myeloid-derived suppressor cell (MDSC). Therefore, the MDSC has been identified as a potential biomarker for PMN formation, the detection of which would enable clinicians to proactively treat metastases. However, there is currently no technology capable of the in situ detection of MDSCs available in the clinic. Here, we propose the use of shortwave infrared-emitting nanoprobes for the tracking of MDSCs and identification of the PMN. Our rare-earth albumin nanocomposites (ReANCs) are engineered to bind the Gr-1 surface marker of murine MDSCs. When delivered intravenously in murine models of breast cancer with high rates of metastasis, the targeted ReANCs demonstrated an increase in localization to the lungs in comparison to control ReANCs. However, no difference was seen in the model with slower rates of metastasis. This highlights the potential utility of MDSC-targeted nanoprobes to assess PMN development and prognosticate disease progression.

Snapshot 3D optical coherence tomography system using image mapping spectrometry.

A snapshot 3-Dimensional Optical Coherence Tomography system was developed using Image Mapping Spectrometry. This system can give depth information (Z) at different spatial positions (XY) within one camera integration time to potentially reduce motion artifact and enhance throughput. The current (x,y,λ) datacube of (85×356×117) provides a 3D visualization of sample with 400 µm depth and 13.4 µm in transverse resolution. Axial resolution of 16.0 µm can also be achieved in this proof-of-concept system. We present an analysis of the theoretical constraints which will guide development of future systems with increased imaging depth and improved axial and lateral resolutions.

Oral triptans and nausea: treatment considerations in migraine.

OBJECTIVE: The objective of this paper is to review evidence showing that migraine patients who are nauseated before using oral triptans tend to have a poor treatment response, as well as to establish a framework for further investigation of the association between response to oral medications and pretreatment nausea among migraineurs. SYNTHESIS AND CONCLUSION: In patients with migraine, pretreatment nausea predicts a poor response to oral triptans. This finding may be inherent in the oral route of delivery of medication, as pretreatment nausea is associated with gastric stasis, which can impair absorption of oral medications and reduce therapeutic efficacy. In addition, oral triptans contribute to the development of nausea among migraine patients who are nausea free before they treat, perhaps because oral tablet use triggers or exacerbates nausea in the same manner as eating or drinking among patients who are nauseated or vulnerable to nausea. Importantly, these observations are derived from a small evidence base and post-hoc analyses or, in the case of treatment-emergent nausea, adverse event reports. Further assessment of the relationships between nausea and oral triptans is necessary before drawing firm conclusions. Should these observations be validated, the use of oral triptans in migraine attacks with nausea or in patients prone to nausea should be reevaluated. Novel routes of administration for triptans allow patients to receive the benefits of migraine-specific therapy even when oral therapy is suboptimal.

Sumatriptan iontophoretic transdermal system: history, study results, and use in clinical practice.

Nausea is a common symptom of migraine, and current treatment guidelines recommend non-oral formulations for nauseated or vomiting patients. Transdermal delivery of sumatriptan, a 5-hydroxytryptamine1B1D agonist with established efficacy in patients with migraine, represents a novel approach to acute treatment. The sumatriptan iontophoretic transdermal system circumvents the gastrointestinal tract by using low-level electrical energy to transport sumatriptan across the skin. In multiple well-controlled studies, the sumatriptan transdermal system has shown that it provides consistent drug delivery with low interpatient variability, rapid relief of migraine pain and associated symptoms, and an excellent overall safety profile, with a low incidence of triptan-sensation adverse events. Patients and health care professionals who have used the sumatriptan transdermal system give it high ratings for ease of use/application. The sumatriptan transdermal system will allow a wide range of patients, especially those who experience migraine-related nausea or vomiting, to receive the benefits of migraine-specific therapy.

Special Section Guest Editorial: Short Wave Infrared Techniques and Applications in Biomedical Optics.

The editorial introduces the JBO Special Section on Short Wave Infrared Techniques and Applications in Biomedical Optics.

Discrimination of benign and neoplastic mucosa with a high-resolution microendoscope (HRME) in head and neck cancer.

BACKGROUND: The efficacy of ablative surgery for head and neck squamous cell carcinoma (HNSCC) depends critically on obtaining negative margins. Although intraoperative "frozen section" analysis of margins is a valuable adjunct, it is expensive, time-consuming, and highly dependent on pathologist expertise. Optical imaging has potential to improve the accuracy of margins by identifying cancerous tissue in real time. Our goal was to determine the accuracy and inter-rater reliability of head and neck cancer specialists using high-resolution microendoscopic (HRME) images to discriminate between cancerous and benign mucosa. METHODS: Thirty-eight patients diagnosed with head and neck squamous cell carcinoma (HNSCC) were enrolled in this single-center study. HRME was used to image each specimen after application of proflavine, with concurrent standard histopathologic analysis. Images were evaluated for quality control, and a training set containing representative images of benign and neoplastic tissue was assembled. After viewing training images, seven head and neck cancer specialists with no previous HRME experience reviewed 36 test images and were asked to classify each. RESULTS: The mean accuracy of all reviewers in correctly diagnosing neoplastic mucosa was 97% (95% confidence interval (CI), 94-99%). The mean sensitivity and specificity were 98% (97-100%) and 92% (87-98%), respectively. The Fleiss kappa statistic for inter-rater reliability was 0.84 (0.77-0.91). CONCLUSIONS: Medical professionals can be quickly trained to use HRME to discriminate between benign and neoplastic mucosa in the head and neck. With further development, the HRME shows promise as a method of real-time margin determination at the point of care.

Feasibility and preliminary accuracy of high-resolution imaging of the liver and pancreas using FNA compatible microendoscopy (with video).

BACKGROUND: EUS-guided FNA is one of the few techniques that can obtain cells and tissue from the liver and pancreas. However, the technique remains vulnerable to poor specimen quality and sampling error. OBJECTIVE: To evaluate the ability of a high-resolution microendoscope (HRME) to visualize the cellular and architectural features of normal and malignant liver and pancreatic tissue ex vivo, to assess the ability of endosonographers to identify normal and neoplastic tissue by using HRME images, and to demonstrate preliminary technical feasibility of in vivo HRME imaging via EUS fine-needle puncture (FNP). DESIGN: Ex vivo pilot feasibility study in human tissue; in vivo swine model. SETTING: Two academic medical centers. PATIENTS: Co-registered HRME images and biopsies were obtained from surgically resected hepatic and pancreatic tissues from 44 patients. INTERVENTION: Images were divided into training (12 images) and test (80 images) sets containing a range of normal and pathologic conditions for each organ. After viewing the training sets, 9 endosonographers attempted to distinguish malignant tissue from normal or benign lesions in the test sets, each of which contained 40 unique images with individual diagnoses from pathology. MAIN OUTCOME MEASUREMENTS: Image acquisition feasibility, ex vivo and in vivo. Ability of endosonographers to recognize features of normal/benign or malignant tissue from the liver and pancreas. RESULTS: Overall, the 9 endosonographers achieved median accuracy figures of 85% in the liver and 90% in the pancreas. The endosonographers with prior experience in reading HRME images achieved accuracy rates between 90% and 95%. Technical feasibility of HRME imaging through a 19-gauge EUS-FNP needle was demonstrated in an in vivo swine model. LIMITATIONS: Ex vivo study. CONCLUSION: High-resolution microendoscopy allows real-time imaging of cellular-level morphology and tissue architecture in the liver and pancreas. The technique appears to have a short learning curve, after which endosonographers achieved high accuracy rates in distinguishing malignant tissue from normal and benign pathology in both organs. Translating this imaging platform to the in vivo setting appears technically feasible.