Evaluation of the dosimetric and radiobiological parameters in four radiotherapy regimens for synchronous bilateral breast cancer.

This study is to investigate the optimal treatment option for synchronous bilateral breast cancer (SBBC) by comparing dosimetric and radiobiological parameters of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans using single and dual isocenters. Twenty patients with SBBC without lymph node involvement were selected retrospectively. Four treatment plans were generated for each patient using the Eclipse treatment planning system (Varian Medical System, Palo Alto, CA, USA) following two delivery techniques with two isocenter conditions-IMRT using a single isocenter (IMRT_Iso1), VMAT using a single isocenter (VMAT_Iso1), IMRT using dual isocenters (IMRT_Iso2), and VMAT using dual isocenters (VMAT_Iso2). A dose of 42.56 Gy in 16 fractions was prescribed for the planning target volume (PTV). All plans were calculated using the Acuros XB algorithm and a photon optimizer for a 6-MV beam of a Vital Beam linear accelerator. PTV-related dosimetric parameters were analyzed. Further, the homogeneity index, conformity index, and conformation number were computed to evaluate plan quality. Dosimetric parameters were also measured for the organs at risk (OARs). In addition, the equivalent uniform dose corresponding to an equivalent dose related to a reference of 2 Gy per fraction, the tumor control probability, and the normal tissue complication probability were calculated based on the dose-volume histogram to investigate the radiobiological impact on PTV and OARs. IMRT_Iso1 exhibited similar target coverage and a certain degree of dosimetric improvement in OAR sparing compared to the other techniques. It also exhibited some radiobiological improvement, albeit insignificant. Although IMRT_Iso1 significantly increased monitor unit compared to VMAT_Iso1, which is the best option in terms of delivery efficiency, there was only a 22% increase in delivery time. Therefore, in conclusion, IMRT_Iso1, the complete treatment of which can be completed using a single setup, is the most effective method for treating SBBC.

Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ.

Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions.

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.

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.).

Micro-anatomical quantitative optical imaging: toward automated assessment of breast tissues.

INTRODUCTION: Pathologists currently diagnose breast lesions through histologic assessment, which requires fixation and tissue preparation. The diagnostic criteria used to classify breast lesions are qualitative and subjective, and inter-observer discordance has been shown to be a significant challenge in the diagnosis of selected breast lesions, particularly for borderline proliferative lesions. Thus, there is an opportunity to develop tools to rapidly visualize and quantitatively interpret breast tissue morphology for a variety of clinical applications. METHODS: Toward this end, we acquired images of freshly excised breast tissue specimens from a total of 34 patients using confocal fluorescence microscopy and proflavine as a topical stain. We developed computerized algorithms to segment and quantify nuclear and ductal parameters that characterize breast architectural features. A total of 33 parameters were evaluated and used as input to develop a decision tree model to classify benign and malignant breast tissue. Benign features were classified in tissue specimens acquired from 30 patients and malignant features were classified in specimens from 22 patients. RESULTS: The decision tree model that achieved the highest accuracy for distinguishing between benign and malignant breast features used the following parameters: standard deviation of inter-nuclear distance and number of duct lumens. The model achieved 81 % sensitivity and 93 % specificity, corresponding to an area under the curve of 0.93 and an overall accuracy of 90 %. The model classified IDC and DCIS with 92 % and 96 % accuracy, respectively. The cross-validated model achieved 75 % sensitivity and 93 % specificity and an overall accuracy of 88 %. CONCLUSIONS: These results suggest that proflavine staining and confocal fluorescence microscopy combined with image analysis strategies to segment morphological features could potentially be used to quantitatively diagnose freshly obtained breast tissue at the point of care without the need for tissue preparation.

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.

Novel three-dimensional imaging volumetry in autosomal dominant polycystic kidney disease: comparison with 2D volumetry.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) volumetry is an important marker for evaluating the progression of disease. Three-dimensional (3D) volumetry is generally more timesaving than 2D volumetry, but its reliability and accuracy are uncertain. METHODS: Small and large phantoms simulating polycystic kidneys and 20 patients with ADPKD underwent magnetic resonance imaging (MRI) volumetry. We evaluated the total kidney volume (TKV) and total cyst volume (TCV) using a novel 3D volumetry program (XelisTM) and compared 3D volumetry data with the conventional 2D method (the reference volume values). After upload and threshold setting, the other organs surrounding the kidney were removed by picking and sculpting. The novel method involves drawing of the kidney or cyst and automatic measurement of kidney volume and cyst volume in 3D images. RESULTS: The 3D volume estimation of the small and large phantoms differed from the actual values by 6.9% and -8.2%, respectively, for TKV and by 2.1% and 1.4% for TCV. In ADPKD patients, the intra-reader reliability of 3D volumetry was 30 ± 180 mL (1.3 ± 10.3%) and 25 ± 113 mL (1.2 ± 9.4%), respectively, for TKV and TCV. Correlation between 3D volumetry and 2D volumetry of TKV and TCV resulted in a high correlation coefficient and a regression slope approaching 1.00 (r = 0.97 - 0.98). The mean of the volume percentage differences for 3D vs. 2D for TKV : TCV were -6.0 ± 8.9% : 2.0 ± 11.8% in large ADPKD and -16.1 ± 10.4% : 13.2 ± 21.9% in small ADPKD. CONCLUSION: Our study showed that 3D volumetry has reliability and accuracy compared with 2D volumetry in ADPKD. 3D volumetry is more accurate for TCV and large ADPKD.

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.

Advances in fluorescence imaging techniques to detect oral cancer and its precursors.

Oral cancer is a significant health problem in the USA and throughout the world. Most oral cancer patients are diagnosed at a late stage, when treatment is less successful and treatment-associated morbidity is more severe. A number of new diagnostic aids to conventional oral examination have recently been introduced to assist in the early detection of oral neoplasia. In particular, autofluorescence imaging has emerged as a promising adjunctive technique to improve early identification of oral premalignant lesions. Direct visual inspection of tissue autofluorescence has shown encouraging results in high-prevalence populations, but the technique requires subjective interpretation and depends on the visual recognition skills of the examiner. Capturing and analyzing digital fluorescence images can reduce subjectivity and potentially improve sensitivity of detection of precancerous changes. Recent studies of wide-field autofluorescence imaging in low-prevalence populations suggest that benign lesions such as inflammation may give rise to false-positive results. High-resolution fluorescence imaging is a new modality that can be used in conjunction with wide-field imaging to improve specificity by imaging subcellular detail of neoplastic tissues. The combination of wide-field and high-resolution fluorescence imaging systems with automated image analysis should be investigated to maximize overall diagnostic performance for early detection of oral neoplasia.

Effect of chronic unloading and rehabilitation on human Achilles tendon properties: a velocity-encoded phase-contrast MRI study.

The objective of this study was to measure and monitor changes in Achilles tendon mechanical properties and force production capability of triceps surae muscles after 4 wk of limb suspension and 6 wk of physical rehabilitation. Five healthy volunteers underwent unilateral lower limb suspension followed by weekly physiotherapy. A velocity-encoded, phase-contrast magnetic resonance imaging (VE-PC-MRI) technique was used to estimate the tendon strain as a function of force produced during the submaximal isometric contractions. After limb suspension, triceps surae muscle strength decreased to 53.2 +/- 15.6% (mean +/- SD) of the presuspension level (P < 0.05). Young's modulus, estimated from the slope of the tendon stress-strain relationship, decreased by 17.1% (from 140.50 +/- 29.33 to 119.95 +/- 36.07 MPa, P < 0.05), while the tendon transition point, reflecting the "toe region," increased by 55.7% (from 2.2 +/- 1.0% to 3.4 +/- 1.24%). Muscle strength, tendon stiffness, and transition point recovered to presuspension levels by the end of 6 wk of rehabilitation. Calcaneus movement was significant during the "isometric" contraction, accounting for 52.13 +/- 7.63% of the tendon displacement. Tendon cross-sectional area determined from anatomic magnetic resonance axial images remained unchanged, suggesting that the altered tendon elastic modulus and transition point were largely due to material deterioration. The increase in the transition point following chronic unloading as measured by the VE-PC-MRI technique has not been previously reported and offers new insights into the biomechanical changes that may occur in the tendon crimp structure.

Phase-contrast MRI reveals mechanical behavior of superficial and deep aponeuroses in human medial gastrocnemius during isometric contraction.

The behavior of the entire medial gastrocnemius (MG) superficial and deep aponeurosis structure was investigated with velocity-encoded phase-contrast, spin-tag, and three-dimensional morphometric magnetic resonance imaging. The displacements and strain of both these aponeuroses, muscle length, and the cross-sectional segment length of the deep aponeurosis were measured during isometric plantarflexion at 20% and 40% of maximal voluntary contraction (MVC). The length of the entire MG shortened during 20% and 40% MVC. All regions of interest in both aponeuroses moved proximally. Positive strain (lengthening) occurred in both ends of the deep aponeurosis and in the proximal region of the superficial aponeurosis. In contrast, negative strain (shortening) was observed in the middle region of the deep aponeurosis and in the distal region of the superficial aponeurosis. Consistent with this shortening of the deep aponeurosis length along the proximal-distal axis was expansion of the aponeuroses in the medial-lateral and anterior-posterior directions in the cross-sectional plane. It is concluded that at low to moderate force levels of isometric contraction, regional differences in strain occur along the proximal-distal axis of both aponeuroses, and some regions of both aponeuroses shorten.

Chemically Homogeneous and Thermally Robust Ni1-xPtxSi Film Formed Under a Non-Equilibrium Melting/Quenching Condition.

To synthesize a thermally robust Ni1-xPtxSi film suitable for ultrashallow junctions in advanced metal-oxide-semiconductor field-effect transistors, we used a continuous laser beam to carry out millisecond annealing (MSA) on a preformed Ni-rich silicide film at a local surface temperature above 1000 °C while heating the substrate to initiate a phase transition. The melting and quenching process by this unique high-temperature MSA process formed a Ni1-xPtxSi film with homogeneous Pt distribution across the entire film thickness. After additional substantial thermal treatment up to 800 °C, the noble Ni1-xPtxSi film maintained a low-resistive phase without agglomeration and even exhibited interface flattening with the underlying Si substrate.

A single port surgical robot system with novel elbow joint mechanism for high force transmission.

BACKGROUND: Despite its evident clinical benefits, single-incision laparoscopic surgery (SILS) imposes inherent limitations of collision between external arms and inadequate triangulation because multiple instruments are inserted through a single port at the same time. METHODS: A robot platform appropriate for SILS was developed wherein an elbowed instrument can be equipped to easily create surgical triangulation without the interference of robot arms. A novel joint mechanism for a surgical instrument actuated by a rigid link was designed for high torque transmission capability. RESULTS: The feasibility and effectiveness of the robot was checked through three kinds of preliminary tests: payload, block transfer, and ex vivo test. Measurements showed that the proposed robot has a payload capability >15 N with 7 mm diameter. CONCLUSIONS: The proposed robot is effective and appropriate for SILS, overcoming inadequate triangulation and improving workspace and traction force capability.

In vivo cytological observation of liver and spleen by using high-resolution microendoscopy system under endoscopic ultrasound guidance: A preliminary study using a swine model.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is useful to obtain specimens from lesions underlying deep parts of the liver and spleen. However, the development of novel ancillary techniques must be explored to reduce the number of needle passes and potential adverse effects during this procedure. We conducted an animal study using a swine to demonstrate technical feasibility of in vivo cytological observation of liver and spleen using the high-resolution microendoscopy (HRME) system under EUS guidance. We successfully performed the study. No significant acute adverse events occurred during the procedure. The HRME system could obtain clear images representing cytology-level morphology of spleen and liver. Hence, it is found out that in vivo cytological observation of liver and spleen using the HRME system under EUS guidance is technically feasible.

Automated frame selection process for high-resolution microendoscopy.

We developed an automated frame selection algorithm for high-resolution microendoscopy video sequences. The algorithm rapidly selects a representative frame with minimal motion artifact from a short video sequence, enabling fully automated image analysis at the point-of-care. The algorithm was evaluated by quantitative comparison of diagnostically relevant image features and diagnostic classification results obtained using automated frame selection versus manual frame selection. A data set consisting of video sequences collected in vivo from 100 oral sites and 167 esophageal sites was used in the analysis. The area under the receiver operating characteristic curve was 0.78 (automated selection) versus 0.82 (manual selection) for oral sites, and 0.93 (automated selection) versus 0.92 (manual selection) for esophageal sites. The implementation of fully automated high-resolution microendoscopy at the point-of-care has the potential to reduce the number of biopsies needed for accurate diagnosis of precancer and cancer in low-resource settings where there may be limited infrastructure and personnel for standard histologic analysis.

Feasibility of bilateral crossing c7 intralaminar screws: a cadaveric study.

OBJECTIVE: When the pedicle screw insertion technique is failed or not applicable, C7 intralaminar screw insertion method has been used as an alternative or salvage fixation method recently. However, profound understanding of anatomy is required for safe application of the bilaterally crossing laminar screw at C7 in clinic. In this cadaveric study, we evaluated the anatomic feasibility of the bilateral crossing intralaminar screw insertion and especially focused on determination of proper screw entry point. METHODS: The C7 vertebrae from 18 adult specimens were studied. Morphometric measurements of the mid-laminar height, the minimum laminar thickness, the maximal screw length, and spino-laminar angle were performed and cross-sectioned vertically at the screw entry point (spino-laminar junction). The sectioned surface was equally divided into 3 parts and maximal thickness and surface area of the parts were measured. All measurements were obtained bilaterally. RESULTS: The mean mid-laminar height was 13.7 mm, mean minimal laminar thickness was 6.6 mm, mean maximal screw length was 24.6 mm, and mean spinolaminar angle was 50.8±4.7°. Based on the measured laminar thickness, the feasibility of 3.5 mm diameter intralaminar screw application was 83.3% (30 sides laminae out of total 36) when assuming a tolerance of 1 mm on each side. Cross-sectional measurement results showed that the mean maximal thickness of upper, middle, and lower thirds was 5.0 mm, 7.5 mm, and 7.3 mm, respectively, and mean surface area for each part was 21.2 mm(2), 46.8 mm(2), and 34.7 mm(2), respectively. Fourteen (38.9%) sides of laminae would be feasible for 3.5 mm intralaminar screw insertion when upper thirds of C7 spino-laminar junction is the screw entry point. In case of middle and lower thirds of C7 spino-laminar junction, 32 (88.9%) and 28 (77.8%) sides of laminae were feasible for 3.5 mm screw insertion, respectively. CONCLUSION: The vertical cross-sectioned area of middle thirds at C7 spinolaminar junction was the largest area and 3.5 mm screw can be accommodated with 77.8% of feasibility when lower thirds were the screw entry point. Thus, selection of middle and lower thirds for each side of screw entry point in spino-laminar junction would be the safest way to place bilateral crossing laminar screw within the entire lamina. This anatomic study result will help surgeons to place the screw safely and accurately.

Endoscopic ultrasound-assisted direct peritoneal visualization with a small-caliber scope: A proof of concept study in a swine model.

BACKGROUND: Laparoscopic and natural orifice transluminal endoscopic surgery techniques can diagnose peritoneal findings that suggest tumor cell dissemination. However, they have not been incorporated into routine practice, mainly owing to their complexity. To develop a minimally invasive endoscopic technique for the diagnosis of peritoneal findings, we conducted feasibility study using an acute swine model. MATERIALS AND METHODS: This study involved six domestic pigs. Trans-gastric access to the peritoneal cavity was performed utilizing an endoscopic ultrasound fine needle aspiration (EUS-FNA) technique. After dilation of the needle hole with a biliary dilatation catheter and balloon, a small-caliber scope was inserted into the peritoneal cavity. Peritoneal images were obtained with the scope and a high-resolution microendoscope (HRME). Main outcome measurements were technical feasibility and time needed to access the peritoneal cavity. RESULTS: Direct visualization of the peritoneum was successful in all six pigs and gained access to the gross appearance of the peritoneal cavity. HRME imaging with topical contrast agent also obtained reasonable quality images representing nuclei of the peritoneal mesothelium. Average operation time from the initiation of EUS-FNA to acquiring peritoneal images was 26.5 min (range 15-40 min). Autopsy found no damage to the adjacent organs, and stomach wall defects were tightly closed with hemostasis clips. CONCLUSION: EUS-assisted direct peritoneal visualization with small-caliber scope is technically feasible. HRME may assist in the diagnosis of findings on the peritoneum.

Aspergillus Tracheobronchitis and Influenza A Co-infection in a Patient with AIDS and Neutropenia.

Aspergillus tracheobronchitis (AT), an unusual form of invasive pulmonary aspergillosis (IPA), is characterized by pseudomembrane formation, ulcer or obstruction that is predominantly confined to tracheobronchial tree. Hematologic malignancies, neutropenia, solid organ transplantation, chronic corticosteroid therapy and acquired immunodeficiency syndrome (AIDS) are known to be major predisposing conditions. However, since the introduction of highly active antiretroviral therapy, there is only one reported case of AT in AIDS patient. After pandemic of influenza A/H1N1 2009, there are several reports of IPA in patient with influenza and most of them received corticosteroid or immunosuppressive therapy before the development of IPA. We present a 45 year-old AIDS patient with influenza A infection who developed pseudomembranous AT without corticosteroid use or immunosuppressive therapy.

A fiber-optic fluorescence microscope using a consumer-grade digital camera for in vivo cellular imaging.

BACKGROUND: Early detection is an essential component of cancer management. Unfortunately, visual examination can often be unreliable, and many settings lack the financial capital and infrastructure to operate PET, CT, and MRI systems. Moreover, the infrastructure and expense associated with surgical biopsy and microscopy are a challenge to establishing cancer screening/early detection programs in low-resource settings. Improvements in performance and declining costs have led to the availability of optoelectronic components, which can be used to develop low-cost diagnostic imaging devices for use at the point-of-care. Here, we demonstrate a fiber-optic fluorescence microscope using a consumer-grade camera for in vivo cellular imaging. METHODS: The fiber-optic fluorescence microscope includes an LED light, an objective lens, a fiber-optic bundle, and a consumer-grade digital camera. The system was used to image an oral cancer cell line labeled with 0.01% proflavine. A human tissue specimen was imaged following surgical resection, enabling dysplastic and cancerous regions to be evaluated. The oral mucosa of a healthy human subject was imaged in vivo, following topical application of 0.01% proflavine. FINDINGS: The fiber-optic microscope resolved individual nuclei in all specimens and tissues imaged. This capability allowed qualitative and quantitative differences between normal and precancerous or cancerous tissues to be identified. The optical efficiency of the system permitted imaging of the human oral mucosa in real time. CONCLUSION: Our results indicate this device as a useful tool to assist in the identification of early neoplastic changes in epithelial tissues. This portable, inexpensive unit may be particularly appropriate for use at the point-of-care in low-resource settings.

High-resolution fiber optic microscopy with fluorescent contrast enhancement for the identification of axillary lymph node metastases in breast cancer: a pilot study.

This prospective pilot study evaluates the potential of high-resolution fiber optic microscopy (HRFM) to identify lymph node metastases in breast cancer patients. 43 lymph nodes were collected from 14 consenting breast cancer patients. Proflavine dye was topically applied to lymph nodes ex vivo to allow visualization of nuclei. 242 images were collected at 105 sites with confirmed histopathologic diagnosis. Quantitative statistical features were calculated from images, assessed with one-way ANOVA, and were used to develop a classification algorithm with the goal of objectively discriminating between normal and metastatic tissue. A classification algorithm using mean image intensity and skewness achieved sensitivity of 79% (27/34) and specificity of 77% (55/71). This study demonstrates the technical feasibility and diagnostic potential of HRFM with fluorescent contrast in the ex vivo evaluation of lymph nodes from breast cancer patients.