Segmenting Skin Biopsy Images with Coarse and Sparse Annotations using U-Net.

The number of melanoma diagnoses has increased dramatically over the past three decades, outpacing almost all other cancers. Nearly 1 in 4 skin biopsies is of melanocytic lesions, highlighting the clinical and public health importance of correct diagnosis. Deep learning image analysis methods may improve and complement current diagnostic and prognostic capabilities. The histologic evaluation of melanocytic lesions, including melanoma and its precursors, involves determining whether the melanocytic population involves the epidermis, dermis, or both. Semantic segmentation of clinically important structures in skin biopsies is a crucial step towards an accurate diagnosis. While training a segmentation model requires ground-truth labels, annotation of large images is a labor-intensive task. This issue becomes especially pronounced in a medical image dataset in which expert annotation is the gold standard. In this paper, we propose a two-stage segmentation pipeline using coarse and sparse annotations on a small region of the whole slide image as the training set. Segmentation results on whole slide images show promising performance for the proposed pipeline.

Characterization of multiple diagnostic terms in melanocytic skin lesion pathology reports.

BACKGROUND: Histopathologically ambiguous melanocytic lesions lead some pathologists to list multiple diagnostic considerations in the pathology report. The frequency and circumstance of multiple diagnostic considerations remain poorly characterized. METHODS: Two hundred and forty skin biopsy samples were interpreted by 187 pathologists (8976 independent diagnoses) and classified according to a diagnostic/treatment stratification (MPATH-Dx). RESULTS: Multiple diagnoses in different MPATH-Dx classes were used in n = 1320 (14.7%) interpretations, with 97% of pathologists and 91% of cases having at least one such interpretation. Multiple diagnoses were more common for intermediate risk lesions and are associated with greater subjective difficulty and lower confidence. We estimate that 6% of pathology reports for melanocytic lesions in the United States contain two diagnoses of different MPATH-Dx prognostic classes, and 2% of cases are given two diagnoses with significant treatment implications. CONCLUSIONS: Difficult melanocytic diagnoses in skin may necessitate multiple diagnostic considerations; however, as patients increasingly access their health records and retrieve pathology reports (as mandated by US law), uncertainty should be expressed unambiguously.

Melanoma in the Blink of an Eye: Pathologists' Rapid Detection, Classification, and Localization of Skin Abnormalities.

Expert radiologists can quickly extract a basic "gist" understanding of a medical image following less than a second exposure, leading to above-chance diagnostic classification of images. Most of this work has focused on radiology tasks (such as screening mammography), and it is currently unclear whether this pattern of results and the nature of visual expertise underlying this ability are applicable to pathology, another medical imaging domain demanding visual diagnostic interpretation. To further characterize the detection, localization, and diagnosis of medical images, this study examined eye movements and diagnostic decision-making when pathologists were briefly exposed to digital whole slide images of melanocytic skin biopsies. Twelve resident (N = 5), fellow (N = 5), and attending pathologists (N = 2) with experience interpreting dermatopathology briefly viewed 48 cases presented for 500 ms each, and we tracked their eye movements towards histological abnormalities, their ability to classify images as containing or not containing invasive melanoma, and their ability to localize critical image regions. Results demonstrated rapid shifts of the eyes towards critical abnormalities during image viewing, high diagnostic sensitivity and specificity, and a surprisingly accurate ability to localize critical diagnostic image regions. Furthermore, when pathologists fixated critical regions with their eyes, they were subsequently much more likely to successfully localize that region on an outline of the image. Results are discussed relative to models of medical image interpretation and innovative methods for monitoring and assessing expertise development during medical education and training.

Pathology Trainees' Experience and Attitudes on Use of Digital Whole Slide Images.

Digital whole slide images are Food and Drug Administration approved for clinical diagnostic use in pathology; however, integration is nascent. Trainees from 9 pathology training programs completed an online survey to ascertain attitudes toward and experiences with whole slide images for pathological interpretations. Respondents (n = 76) reported attending 63 unique medical schools (45 United States, 18 international). While 63% reported medical school exposure to whole slide images, most reported ≤ 5 hours. Those who began training more recently were more likely to report at least some exposure to digital whole slide image training in medical school compared to those who began training earlier: 75% of respondents beginning training in 2017 or 2018 reported exposure to whole slide images compared to 54% for trainees beginning earlier. Trainees exposed to whole slide images in medical school were more likely to agree they were comfortable using whole slide images for interpretation compared to those not exposed (29% vs 12%; P = .06). Most trainees agreed that accurate diagnoses can be made using whole slide images for primary diagnosis (92%; 95% CI: 86-98) and that whole slide images are useful for obtaining second opinions (93%; 95% CI: 88-99). Trainees reporting whole slide image experience during training, compared to those with no experience, were more likely to agree they would use whole slide images in 5 years for primary diagnosis (64% vs 50%; P = .3) and second opinions (86% vs 76%; P = .4). In conclusion, although exposure to whole slide images in medical school has increased, overall exposure is limited. Positive attitudes toward future whole slide image diagnostic use were associated with exposure to this technology during medical training. Curricular integration may promote adoption.

Factors associated with use of immunohistochemical markers in the histopathological diagnosis of cutaneous melanocytic lesions.

BACKGROUND: Melanocytic tumors are often challenging and constitute almost one in four skin biopsies. Immunohistochemical (IHC) studies may assist diagnosis; however, indications for their use are not standardized. METHODS: A test set of 240 skin biopsies of melanocytic tumors was examined by 187 pathologists from 10 US states, interpreting 48 cases in Phase I and either 36 or 48 cases in Phase II. Participant and diagnosis characteristics were compared between those who reported they would have ordered, or who would have not ordered IHC on individual cases. Intraobserver analysis examined consistency in the intent to order when pathologists interpreted the same cases on two occasions. RESULTS: Of 187 participants interpreting 48 cases each, 21 (11%) did not request IHC tests for any case, 85 (45%) requested testing for 1 to 6 cases, and 81 (43%) requested testing for ≥6 cases. Of 240 cases, 229 had at least one participant requesting testing. Only 2 out of 240 cases had more than 50% of participants requesting testing. Increased utilization of testing was associated with younger age of pathologist, board-certification in dermatopathology, low confidence in diagnosis, and lesions in intermediate MPATH-Dx classes 2 to 4. The median intraobserver concordance for requesting tests among 72 participants interpreting the same 48 cases in Phases I and II was 81% (IQR 73%-90%) and the median Kappa statistic was 0.20 (IQR 0.00, 0.39). CONCLUSION: Substantial variability exists among pathologists in utilizing IHC.

Trends in sexual orientation missing data over a decade of the California Health Interview Survey.

OBJECTIVES: We explored changes in sexual orientation question item completion in a large statewide health survey. METHODS: We used 2003 to 2011 California Health Interview Survey data to investigate sexual orientation item nonresponse and sexual minority self-identification trends in a cross-sectional sample representing the noninstitutionalized California household population aged 18 to 70 years (n = 182 812 adults). RESULTS: Asians, Hispanics, limited-English-proficient respondents, and those interviewed in non-English languages showed the greatest declines in sexual orientation item nonresponse. Asian women, regardless of English-proficiency status, had the highest odds of item nonresponse. Spanish interviews produced more nonresponse than English interviews and Asian-language interviews produced less nonresponse when we controlled for demographic factors and survey cycle. Sexual minority self-identification increased in concert with the item nonresponse decline. CONCLUSIONS: Sexual orientation nonresponse declines and the increase in sexual minority identification suggest greater acceptability of sexual orientation assessment in surveys. Item nonresponse rate convergence among races/ethnicities, language proficiency groups, and interview languages shows that sexual orientation can be measured in surveys of diverse populations.

Macular features from spectral-domain optical coherence tomography as an adjunct to indirect ophthalmoscopy in retinopathy of prematurity.

PURPOSE: To compare vitreoretinal pathology imaged with portable handheld spectral-domain optical coherence tomography (SD-OCT) to conventional indirect ophthalmoscopic examination in neonates undergoing screening for retinopathy of prematurity. METHODS: Spectral-domain optical coherence tomography images were collected from 76 eyes of 38 neonates during 118 routine retinopathy of prematurity examinations. Imaging sessions in the Neonatal Intensive Care Unit were performed immediately after the subjects underwent a standard ophthalmic examination with indirect ophthalmoscopic by a pediatric ophthalmologist. Masked certified SD-OCT graders evaluated scans for preretinal and retinal findings including material in the vitreous, epiretinal membrane, intraretinal cystoid structures and deposits, optic nerve and vascular features, and severity and location of retinopathy of prematurity. The frequency of detection of these features by clinical examination and evaluation of SD-OCT images was compared to determine potential clinical advantages for each modality. RESULTS: Portable SD-OCT imaging characterized macular features of retinal cystoid structures in 39% of examinations and epiretinal membrane in 32% of examinations. Neither feature was visualized by indirect ophthalmoscopy in any cases. The clinician using indirect ophthalmoscopy detected stage of retinopathy of prematurity and the presence or absence of Plus or pre-Plus disease. These were not visualized with SD-OCT. CONCLUSION: Spectral-domain optical coherence tomography provides new information about the premature infant retina that is of unknown importance relative to visual development and acuity. As used in this study, SD-OCT does not replace indirect ophthalmoscopy for evaluation of retinopathy of prematurity.

Intravitreal triamcinolone acetonide in the treatment of macular retinal detachment associated with morning glory anomaly.

PURPOSE: To report the successful treatment of a case of recurrent macular retinal detachment associated with morning glory anomaly using intravitreal triamcinolone acetonide. METHODS: A 53-year-old man with a history of bilateral morning glory anomaly and recurrent macular detachment of the left eye refractory to multiple surgical interventions, including 3 vitrectomies with endolaser photocoagulation, gas tamponade, and fibrin glue, underwent an intravitreal injection of 4 mg triamcinolone acetonide. RESULTS: A single treatment with intravitreal triamcinolone acetonide resulted in resolution of a macular retinal detachment and intraretinal fluid within 2 weeks. CONCLUSION: Treatment with intravitreal triamcinolone acetonide may be beneficial in cases of macular retinal detachment associated with morning glory anomaly.

Controlled release of nerve growth factor enhances sciatic nerve regeneration.

Based on previous studies demonstrating the potential of growth factors to enhance peripheral nerve regeneration, we developed a novel growth factor delivery system to provide sustained delivery of nerve growth factor (NGF). This delivery system uses heparin to immobilize NGF and slow its diffusion from a fibrin matrix. This system has been previously shown to enhance neurite outgrowth in vitro, and in this study, we evaluated the ability of this delivery system to enhance nerve regeneration through conduits. We tested the effect of controlled NGF delivery on peripheral nerve regeneration in a 13-mm rat sciatic nerve defect. The heparin-containing delivery system was studied in combination with three doses of NGF (5, 20, or 50 ng/mL) and the results were compared with positive controls (isografts) and negative controls (fibrin alone, NGF alone, and empty conduits). Nerves were harvested at 6 weeks postoperatively for histomorphometric analysis. Axonal regeneration in the delivery system groups revealed a marked dose-dependent effect. The total number of nerve fibers at both the mid-conduit level and in the distal nerve showed no statistical difference for NGF doses at 20 and 50 ng/mL from the isograft (positive control). The results of this study demonstrate that the incorporation of a novel delivery system providing controlled release of growth factors enhances peripheral nerve regeneration and represents a significant contribution toward enhancing nerve regeneration across short nerve gaps.