Optical imaging guided- 'precision' biopsy of skin tumors: a novel approach for targeted sampling and histopathologic correlation.

Dermoscopy and reflectance confocal microscopy (RCM) are two noninvasive, optical imaging tools used to facilitate clinical diagnosis. A biopsy technique that produces exact correlation with optical imaging features is not previously reported. To evaluate the applications of a novel feature-focused 'precision biopsy' technique that correlates clinical-dermoscopy-RCM findings with histopathology. This was a prospective case-series performed during August 2017 and June 2019 at a tertiary care cancer. We included consecutive patients requiring a precise dermoscopy-RCM-histopathologic correlation. We performed prebiopsy dermoscopy and both wide probe and handheld RCM of suspicious lesions. Features of interest were isolated with the aid of paper rings and a 2 mm punch biopsy was performed in the dermoscopy- or RCM-highlighted area. Tissue was processed either en face or with vertical sections. One-to-one correlation with histopathology was obtained. Twenty-three patients with 24 lesions were included in the study. The mean age was 64.6 years (range 22-91 years); there were 16 (69.6%) males, 14 (58.3%) lesions biopsied were on head and neck region. We achieved tissue-conservation diagnosis in 100% (24/24), 13 (54.2%) were clinically equivocal lesions, six (25%) were selected for 'feature correlation' of structures on dermoscopy or RCM, and five (20.8%) for 'correlation of new/unknown' RCM features seen on follow-up. The precision biopsy technique described herein is a novel method that facilitates direct histopathological correlation of dermoscopy and RCM features. With the aids of optical imaging devices, accurate diagnosis may be achieved by minimally invasive tissue extraction.

Engineering of Phytosterol-Producing Yeast Platforms for Functional Reconstitution of Downstream Biosynthetic Pathways.

As essential structural molecules for plant plasma membranes, phytosterols are key intermediates for the synthesis of many downstream specialized metabolites of pharmaceutical or agricultural significance, such as brassinosteroids and withanolides. Saccharomyces cerevisiae has been widely used as an alternative producer for plant secondary metabolites. Establishment of heterologous sterol pathways in yeast, however, has been challenging due to either low efficiency or structural diversity, likely a result of crosstalk between the heterologous phytosterol and the endogenous ergosterol biosynthesis. For example, in this study, we engineered campesterol production in yeast using plant enzymes; although we were able to enhance the titer of campesterol to ∼40 mg/L by upregulating the mevalonate pathway, no conversion to downstream products was detected upon the introduction of downstream plant enzymes. Further investigations uncovered two interesting observations about sterol engineering in yeast. First, many heterologous sterols tend to be efficiently and intensively esterified in yeast, which drastically impedes the function of downstream enzymes. Second, yeast can overcome the growth deficiency caused by altered sterol metabolism through repeated culture. By employing metabolic engineering, strain evolution, fermentation engineering, and pathway reconstitution, we were able to reconstruct the multienzyme pathways for the synthesis of a set of phytosterols: campesterol (∼7 mg/L), ß-sitosterol (∼2 mg/L), 22-hydroxycampesterol (∼1 mg/L), and 22-hydroxycampest-4-en-3-one (∼4 mg/L). This work identified and addressed some of the technical bottlenecks in phytosterol-derived pathway reconstitution in the baker's yeast and opens up opportunities for efficient bioproduction and metabolic pathway elucidation of this group of phytochemicals.

Comparison of in situ cone beam computed tomography scan data with ex vivo optical scan data in the measurement of root surface area.

OBJECTIVE: The aim of this study was to compare root surface area (RSA) measurements of single-root teeth in a sheep mandible based on cone beam computed tomography (CBCT) with measurements made with an optical scanner. STUDY DESIGN: Eight anterior teeth of a sheep cadaver mandible were scanned in situ by using CBCT with 3 different exposure parameters, followed by treatment with smoothing software. The teeth were then extracted and scanned individually with an optical scanner. Three-dimensional digital models of the teeth were reconstructed on the basis of CBCT and optical scanner data. RSA data were calculated, and an equivalence test was used to statistically compare the measurements with significance of difference established at α = 0.05. RESULTS: The means of the differences between RSA measurements from CBCT and optical scanning ranged from 0.33% to 3.01%. There were no statistically significant differences between the 2 methods. The smoothing parameters for good fitness of the linear regression were determined to be 0.8 for the smooth factor, 8 for iterations, and 0 for compensate shrinkage. CONCLUSIONS: The proposed CBCT technique to measure RSA is feasible. RSA data obtained from CBCT in situ are as accurate as optical scanner measurements ex vivo.

Topical Aluminum Chloride and Monsel's Solution Block Toluidine Blue Staining in Mohs Frozen Sections: Mechanism and Solution.

BACKGROUND: A diminished-staining artifact is observed in some Mohs frozen sections that are stained in toluidine blue (T-blue). Such an artifact, not yet described in the literature, may interfere with a Mohs surgeon's accurate reading. The authors hypothesize that topical hemostatic agents, aluminum chloride, and Monsel's solution are the causative factors. OBJECTIVE: To evaluate the aforementioned topical hemostatic agents as a potential cause of the nonstaining artifact, to propose the mechanism associated with this phenomenon, and to develop a method to prevent or rectify the problem. MATERIALS AND METHODS: Leftover Mohs frozen sections and specimens were treated with aluminum chloride or Monsel's solution and processed with routine Mohs histology. RESULTS: Nonstaining artifact is reproduced in aluminum chloride or Monsel's solution-treated ex vivo skin specimens. The authors found that ethylenediaminetetraacetic acid (EDTA), a chelating agent, can reverse the staining blockage. Such a finding suggests that aluminum or ferric cations bind to tissue and subsequently inhibit T-blue from interacting with the tissue. Direct binding of ferric cations to the tissue section is demonstrated with Prussian blue iron staining. CONCLUSION: By rinsing Mohs frozen sections in an EDTA solution before T-blue staining, the authors could prevent hemostatic agent-induced nonstaining. Applying an EDTA wash and restaining the slides can correct the same artifact.

SMAP L-Band Microwave Radiometer: Instrument Design and First Year on Orbit.

The Soil Moisture Active-Passive (SMAP) L-band microwave radiometer is a conical scanning instrument designed to measure soil moisture with 4% volumetric accuracy at 40-km spatial resolution. SMAP is NASA's first Earth Systematic Mission developed in response to its first Earth science decadal survey. Here, the design is reviewed and the results of its first year on orbit are presented. Unique features of the radiometer include a large 6-m rotating reflector, fully polarimetric radiometer receiver with internal calibration, and radio-frequency interference detection and filtering hardware. The radiometer electronics are thermally controlled to achieve good radiometric stability. Analyses of on-orbit results indicate that the electrical and thermal characteristics of the electronics and internal calibration sources are very stable and promote excellent gain stability. Radiometer NEDT < 1 K for 17-ms samples. The gain spectrum exhibits low noise at frequencies >1 MHz and 1/f noise rising at longer time scales fully captured by the internal calibration scheme. Results from sky observations and global swath imagery of all four Stokes antenna temperatures indicate that the instrument is operating as expected.

Mandibular inferior cortical bone thickness on panoramic radiographs in patients using bisphosphonates.

OBJECTIVE: The goal of this study was to detect dimensional changes in the mandibular cortical bone associated with bisphosphonate (BP) use and to correlate measurements of the cortical bone with the cumulative dose of BPs. STUDY DESIGN: Mandibular inferior cortical bone thickness (MICBT) was measured under the mental foramen on panoramic radiographs of patients with and without bisphosphonate-related osteonecrosis of the jaws (BRONJ) taking BPs and controls. RESULTS: Patients with BRONJ had the highest mean MICBT (6.81 ± 1.35 mm), compared with patients without BRONJ taking BPs (5.44 ± 1.09 mm) and controls (4.79 ± 0.85 mm) (P < .01). Mean MICBT of patients with BRONJ was significantly higher than that of patients without BRONJ taking BPs. There was a correlation between MICBT and cumulative dose of zolendronate. CONCLUSIONS: Measurement of MICBT on panoramic radiographs is a potentially useful tool for the detection of dimensional changes associated with BP therapy.

Intraoral radiography and dental implant restoration.

The usefulness of IOR has been described along with its limitations when considering implant restorations. One major issue is the alignment of the incident x-rays so that they are consistently perpendicular to the implant body, to provide the most reliable information possible. Other limitations include inconsistencies as a result of the inability to verify the nature and extent of bone around an implant, which is subject to variation as a result of type of bone and site. Where implants are concerned, as a diagnostic tool IOR should be considered as part of a multitude of tests-including probing, mobility, symptoms, and other soft-tissue evaluations. It must be emphasized that IOR cannot be relied upon as being the sole diagnostic test.

Mandibular cortical bone evaluation on cone beam computed tomography images of patients with bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVES: The objective of this study was to develop a technique for detecting cortical bone dimensional changes in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ). STUDY DESIGN: Subjects with BRONJ who had cone-beam computed tomography imaging were selected, with age- and gender-matched controls. Mandibular cortical bone measurements to detect bisphosphonate-related cortical bone changes were made inferior to mental foramen, in 3 different ways: within a fixed sized rectangle, in a rectangle varying with the cortical height, and a ratio between area and height. RESULTS: Twelve BRONJ cases and 66 controls were evaluated. The cortical bone measurements were significantly higher in cases than controls for all 3 techniques. The bone measurements were strongly associated with BRONJ case status (odds ratio 3.36-7.84). The inter-rater reliability coefficients were high for all techniques (0.71-0.90). CONCLUSIONS: Mandibular cortical bone measurement is a potentially useful tool in the detection of bone dimensional changes caused by bisphosphonates.

Evaluating craniofacial asymmetry with digital cephalometric images and cone-beam computed tomography.

INTRODUCTION: The aim of this study was to evaluate craniofacial asymmetry by using 2-dimensional (2D) posteroanterior cephalometric images, 3-dimensional cone-beam computed tomography (CBCT), and physical measurements (gold standard). METHODS: Ten dry human skulls were assessed, and radiopaque markers were placed on 17 skeletal landmarks. Twenty linear measurements were taken on each side to compare the right and left sides and to compare these measurements with the physical measurements made with a digital caliper. To acquire the 2D posteroanterior radiographs, an Extraoral Phosphor Storage Plate (Air Techniques, Chicago, Ill) was used as the image receptor with a Eureka x-ray-Duocon Machlett unit (Machlett Laboratores, Chicago, Ill). Three-dimensional imaging data were acquired from a CB MercuRay (Hitachi Medical, Tokyo, Japan). RESULTS: On average, the right side was larger than the left for most of the 20 distances evaluated in the digital 2D and the CBCT images, and there was poor agreement between the digital 2D images and the physical measurements (kappa = 0.0609) and almost perfect agreement (kappa = 0.92) between the CBCT and physical measurements when individual measurements were considered. CONCLUSIONS: Human skulls, with no apparent asymmetry, had some differences between the right and left sides, with dominance for the right side but with no clinical significance. CBCT can better evaluate craniofacial morphology when compared with digital 2D images.

Bone volume, tooth volume, and incisor relapse: a 3-dimensional analysis of orthodontic stability.

INTRODUCTION: Orthodontic relapse is a common and significant problem. Few risk factors have been identified, and the role of bone has only recently been investigated. The purpose of this study was to examine the influence of alveolar bone volume and tooth volume on dental relapse. METHODS: The sample was chosen from the postretention database at the Department of Orthodontics of the University of Washington in Seattle. Based on the 10-year postretention (T3) irregularity index (II), 40 relapse subjects (T3 II > 6 mm) and the 40 most stable subjects (lowest T3 II < 1.5 mm) were identified for the study. Cone-beam computed tomography (CBCT) scans were taken of the posttreatment (T2) models. Total volume (V) was defined laterally by the distal contact points of the canines and vertically by the cusp tips of the canines to a depth 7 mm below the most inferior gingival margin. Alveolar volume (AV) was defined as the region below a vertical line at the most inferior gingival margin and tooth volume (TV) as the region above that line. The ratio TV:AV was calculated. Logistic regression analysis was used to determine the association between relapse and AV, and to adjust for potentially confounding variables (TV, initial II, sex, age, retention time, and postretention time). Mandibular cortical thickness (CT) measured on T2 lateral cephalograms was used as another measure of bone quantity. Nine patients from the graduate orthodontic clinic who had pretreatment CBCT scans were identified. V, AV, and TV were measured on both the in-vivo scans and the scans of their dental casts to verify the method. RESULTS: The relapse group had significantly greater V and AV and significantly lower CT. TV:AV was not different between the groups. T2 II was found to be a significant predictor of relapse based on logistic regression analysis, whereas AV was not. CT was poorly correlated with AV. V and AV were highly correlated between in-vivo scans and dental cast scans, whereas TV approached significance. CONCLUSIONS: Although postretention relapse was associated with increased V and AV, when other variables were controlled, bone volume was not a significant predictor of relapse.

A descriptive study of the radiographic density of implant restorative cements.

STATEMENT OF PROBLEM: Cementation of implant prostheses is a common practice. Excess cement in the gingival sulcus may harm the periodontal tissues. Identification of the excess cement may be possible with the use of radiographs if the cement has sufficient radiopacity. PURPOSE: The purpose of this study was to compare the radiographic density of different cements used for implant prostheses. MATERIAL AND METHODS: Eight different cements were compared: TempBond Original (TBO), TempBond NE (TBN), Fleck's (FL), Dycal (DY), RelyX Unicem (RXU), RelyX Luting (RXL), Improv (IM), and Premier Implant Cement (PIC). Specimen disks, 2 mm in thickness, were radiographed. Images were made using photostimulable phosphor (PSP) plates with standardized exposure values. The average grey level of the central area of each specimen disk was selected and measured in pixels using a software analysis program, ImageTool, providing an average grey level value representative of radiodensity for each of the 8 cements. The radiodensity was determined using the grey level values of the test materials, which were recorded and compared to a standard aluminum step wedge. An equivalent thickness of aluminum in millimeters was calculated using best straight line fit estimates. To assess contrast effects by varying the exposure settings, a second experiment using 1-mm-thick cement specimens radiographed at both 60 kVp and 70 kVp was conducted. The PSP plates with specimens were measured for a grey level value comparison to the standard aluminum step wedge, using the same software program. RESULTS: The highest grey level values were recorded for the zinc cements (TBO, TBN, and FL), with the 1-mm specimen detectable at both 60- and 70-kVp settings. A lower grey level was recorded for DY, indicative of a lower radiodensity compared to the zinc cements, but higher than RXL and RXU. The implant-specific cements had the lowest grey level values. IM could only be detected in 2-mm-thick sections with a lower aluminum equivalence value than the previously mentioned cements. PIC could not be detected radiographically for either the 1-mm or 2-mm thicknesses at either of the kVp settings. CONCLUSIONS: Some types of cement commonly used for the cementation of implant-supported prostheses have poor radiodensity and may not be detectable following radiographic examination.

Adaptive response of the human dental alveolar process: correction of a Class I protrusive and mutilated dentition, with 32-year follow-up.

A healthy young woman with a severe Class I dental malocclusion and extreme maxillary arch protrusion was treated with conventional edgewise-arch fixed appliance therapy. Four first premolars were removed, and the mandibular second and third molars were moved into positions normally occupied by the mandibular first and second molars. Diagnostic records at ages 17 years 5 months, 22 years 11 months, and 54 years 8 months are presented. (These pretreatment and posttreatment records were presented to the American Board of Orthodontics in 1976 in partial fulfillment of its requirements for the certification process.)

A model for digital archiving of radiographs into a searchable database.

Digital images are routinely used in orthodontic practices today. Many systems and formats are available for producing, storing, retrieving, viewing, and sharing these images. The digital imaging and communication in medicine (DICOM) standard is designed to ensure that these systems and formats are compatible, so that an image produced in a small private practice today can be viewed next year in a large hospital. The purpose of this article is to describe a method for laser scanning and digitization of analog (film) radiographs that meets DICOM standards and allows for web-based archiving, searching, and retrieval.

Cell-based two-region competition algorithm with a map framework for boundary delineation of a series of 2D ultrasound images.

To ensure the delineated boundaries of a series of 2-D images closely following the visually perceivable edges with high boundary coherence between consecutive slices, a cell-based two-region competition algorithm based on a maximum a posteriori (MAP) framework is proposed. It deforms the region boundary in a cell-by-cell fashion through a cell-based two-region competition process. The cell-based deformation is guided by a cell-based MAP framework with a posterior function characterizing the distribution of the cell means in each region, the salience and shape complexity of the region boundary and the boundary coherence of the consecutive slices. The proposed algorithm has been validated using 10 series of breast sonograms, including seven compression series and three freehand series. The compression series contains two carcinoma and five fibroadenoma cases and the freehand series contains two carcinoma and one fibroadenoma cases. The results show that >70% of the derived boundaries fall within the span of the manually delineated boundaries. The robustness of the proposed algorithm to the variation of regions-of-interest is confirmed by the Friedman tests and the p-values of which are 0.517 and 0.352 for the compression and freehand series groups, respectively. The Pearson's correlations between the lesion sizes derived by the proposed algorithm and those defined by the average manually delineated boundaries are all higher than 0.990. The overlapping and difference ratios between the derived boundaries and the average manually delineated boundaries are mostly higher than 0.90 and lower than 0.13, respectively. For both series groups, all assessments conclude that the boundaries derived by the proposed algorithm be comparable to those delineated manually. Moreover, it is shown that the proposed algorithm is superior to the Chan and Vese level set method based on the paired-sample t-tests on the performance indices at a 5% significance level.

Trabecular and cortical bone as risk factors for orthodontic relapse.

INTRODUCTION: Dental relapse of the mandibular incisors after orthodontic treatment is a common problem, and few risk factors have been identified. The purpose of this case-control study was to evaluate whether the amount or the structure of mandibular bone affects the potential for postorthodontic mandibular incisor relapse. METHODS: The subject sample was selected from the postretention database at the University of Washington. Subjects were chosen based on the availability of lateral cephalograms and mandibular periapical radiographs taken approximately 10 years postretention (T3). The mandibular incisor irregularity index (II) was measured on the T3 casts. Two groups were identified: subjects with the II greater than 6 mm (relapse or case) and those with the II less than 3.5 mm (stable or control). Once the case/control status was determined, the II was measured on models taken at the initial orthodontic examination (T1) and at the end of treatment (T2). Sixty relapse and 263 stable subjects were identified. Mandibular cortical thickness measured on both panoramic and lateral cephalometric radiographs was used to assess the amount of mandibular bone, and fractal analysis was used to analyze the trabecular bone structure around the mandibular incisors on the periapical radiographs. Logistic regression analyses were used to determine the association between dental relapse and significant bone parameters. The models were adjusted for potentially confounding variables (initial II, sex, age, and postretention time). RESULTS: The relapse subjects had a larger mean II at T1 and a longer postretention time than the stable subjects. The mean cephalometric mandibular cortical thickness was significantly smaller in the relapse group than in the stable group at T1, T2, and T3. There were no statistically significant differences in the trabecular structure of bone, as measured with fractal analyses, between the relapse and stable groups. CONCLUSIONS: These results indicate that patients with thinner mandibular cortices are at increased risk for dental relapse.

Cell-competition algorithm: a new segmentation algorithm for multiple objects with irregular boundaries in ultrasound images.

Segmentation of multiple objects with irregular contours and surrounding sporadic spots is a common practice in ultrasound image analysis. A new region-based approach, called cell-competition algorithm, is proposed for simultaneous segmentation of multiple objects in a sonogram. The algorithm is composed of two essential ideas. One is simultaneous cell-based deformation of regions and the other is cell competition. The cells are generated by two-pass watershed transformations. The cell-competition algorithm has been validated with 13 synthetic images of different contrast-to-noise ratios and 71 breast sonograms. Three assessments have been carried out and the results show that the boundaries derived by the cell-competition algorithm are reasonably comparable to those delineated manually. Moreover, the cell-competition algorithm is robust to the variation of regions-of-interest and a range of thresholds required for the second-pass watershed transformation. The proposed algorithm is also shown to be superior to the region-competition algorithm for both types of images.