Ultrasound-Guided Optical Tomographic Imaging of Malignant and Benign Breast Lesions: Initial Clinical Results of 19 Cases

AbstractThe diagnosis of solid benign and malignant tumors presents a unique challenge to all noninvasive imaging modalities. Ultrasound is used in conjunction with mammography to differentiate simple cysts from solid lesions. However, the overlapping appearances of benign and malignant lesions make ultrasound less useful in differentiating solid lesions, resulting in a large number of benign biopsies. Optical tomography using near-infrared diffused light has great potential for imaging functional parameters of 1) tumor hemoglobin concentration, 2) oxygen saturation, 3) metabolism, as well as other tumor distinguishing characteristics. These parameters can differentiate benign from malignant lesions. However, optical tomography, when used alone, suffers from low spatial resolution and target localization uncertainty due to intensive light scattering. Our aim is to combine diffused light imaging with ultrasound in a novel way for the detection and diagnosis of solid lesions. Initial findings of two earlystage invasive carcinomas, one combined fibroadenoma and fibrocystic change with scattered foci of lobular neoplasia/lobular carcinoma in situ, 16 benign lesions are reported in this paper. The invasive cancer cases reveal about two-fold greater total hemoglobin concentration (mean 119 μmol) than benign cases (mean 67 μmol), suggest that the discrimination of benign and malignant breast lesions might be enhanced by this type of achievable optical quantification with ultrasound localization. Furthermore, the small invasive cancers are well localized and have wavelength-dependent appearance in optical absorption maps, whereas the benign lesions appear diffused and relatively wavelength-independent

Identifying an early treatment window for predicting breast cancer response to neoadjuvant chemotherapy using immunohistopathology and hemoglobin parameters

Background Breast cancer pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) varies with tumor subtype. The purpose of this study was to identify an early treatment window for predicting pCR based on tumor subtype, pretreatment total hemoglobin (tHb) level, and early changes in tHb following NAC. Methods Twenty-two patients (mean age 56 years, range 34–74 years) were assessed using a near-infrared imager coupled with an Ultrasound system prior to treatment, 7 days after the first treatment, at the end of each of the first three cycles, and before their definitive surgery. Pathologic responses were dichotomized by the Miller-Payne system. Tumor vascularity was assessed from tHb; vascularity changes during NAC were assessed from a percentage tHb normalized to the pretreatment level (%tHb). After training the logistic prediction models using the previous study data, we assessed the early treatment window for predicting pathological response according to their tumor subtype (human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), triple-negative (TN)) based on tHb, and %tHb measured at different cycles and evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). Results In the new study cohort, maximum pretreatment tHb and %tHb changes after cycles 1, 2, and 3 were significantly higher in responder Miller-Payne 4–5 tumors (n = 13) than non-or partial responder Miller-Payne 1–3 tumors (n = 9). However, no significance was found at day 7. The AUC of the predictive power of pretreatment tHb in the cohort was 0.75, which was similar to the performance of the HER2 subtype as a single predictor (AUC of 0.78). A greater predictive power of pretreatment tHb was found within each subtype, with AUCs of 0.88, 0.69, and 0.72, in the HER2, ER, and TN subtypes, respectively. Using pretreatment tHb and cycle 1 %tHb, AUC reached 0.96, 0.91, and 0.90 in HER2, ER, and TN subtypes, respectively, and 0.95 regardless of subtype. Additional cycle 2 %tHb measurements moderately improved prediction for the HER2 subtype but did not improve prediction for the ER and TN subtypes. Conclusions By combining tumor subtypes with tHb, we predicted the pCR of breast cancer to NAC before treatment. Prediction accuracy can be significantly improved by incorporating cycle 1 and 2 %tHb for the HER2 subtype and cycle 1 %tHb for the ER and TN subtypes

Evaluation of cell-free DNA approaches for multi-cancer early detection

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approaches. The WG methylation feature best predicts cancer signal origin. WG methylation is the most promising technology for MCED and informs development of a targeted methylation MCED test

Finding needles in haystacks: Linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Reannotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi.B.R. and C.L.S. acknowledge support from the Intramural Research Program of the National Institutes of Health, National Library of MedicinePeer Reviewe

Finding needles in haystacks:Linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Reannotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi.The Intramural Research Programs of the National Center for Biotechnology Information, National Library of Medicine and the National Human Genome Research Institute, both at the National Institutes of Health.http://www.ncbi.nlm.nih.gov/bioproject/PRJNA177353am201

Finding needles in haystacks : linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Reannotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi.The Intramural Research Programs of the National Center for Biotechnology Information, National Library of Medicine and the National Human Genome Research Institute, both at the National Institutes of Health.http://www.ncbi.nlm.nih.gov/bioproject/PRJNA177353am201

Noninvasive Monitoring of Breast Cancer during Neoadjuvant Chemotherapy Using Optical Tomography with Ultrasound Localization12

The purposes of this study were 1) to investigate the feasibility of using optical tomography in the near-infrared (NIR) spectrum combined with ultrasound (US) localization (NIR/US) in monitoring tumor vascular changes and assessing tumor pathological response during chemotherapy and 2) to compare the accuracy of NIR/US with magnetic resonance imaging (MRI) in predicting residual cancer after neoadjuvant chemotherapy. Eleven female patients were studied during treatments with a combined imager consisting of a commercially available US system coupled to an NIR imager. Contrast-enhanced MRI was performed before treatment and surgery. Tumor vascular content was assessed based on total hemoglobin concentration and volume obtained from NIR data. A percentage blood volume index (%BVI) was calculated as the percentage ratio of the product of total hemoglobin concentration and volume normalized to pretreatment values. At treatment completion, pathologic assessment revealed three response groups: complete or near-complete responders (A), partial responders (B), and nonresponders (C). The mean %BVIs of groups A, B, and C at the treatment completion were 29.1 ± 6.9%, 46.3 ± 3.7%, and 86.8 ± 30.1%, respectively (differences statistically significant, P < .04). At the end of cycle 2, the %BVI of group A was noticeably lower than that of the partial (P = .091) and nonresponder groups (P = .075). Both NIR/US and MRI were equally effective in distinguishing different response groups in this pilot study. Our initial findings indicate that NIR/US using %BVI can be used during chemotherapy to repeatedly monitor tumor vascular changes. NIR/US also may evaluate pathologic response during treatment allowing for tailoring therapies to response

Tobacco Control at Community Colleges: Context and Opportunities

Introduction Tobacco use among United States college-aged students remains higher than that of the national average. While a majority of public health literature has explained tobacco control programs and policies at traditional four-year colleges and universities, little research exists on programs and policies at two-year community colleges. It is important to understand such efforts at these institutions as they have vastly different infrastructures and enroll a more diverse and at-risk student body compared to traditional four-year colleges. Methods The role of community colleges in health efforts aimed at tobacco use was examined at four community colleges. Qualitative research methods included 18 interviews and four focus groups (N=55), document review, and direct environmental observation. Results Community colleges offered a limited number of tobacco cessation and secondhand smoke prevention initiatives. All colleges provided tobacco control literature, though additional programming varied by college. Indoor and outdoor tobacco use policies existed on all campuses though enforcement was problematic. Little evidence was found that current program and policy approaches are based upon best practices or are being employed successfully. Conclusions Opportunities for best practice strategies for tobacco control were identified for community colleges, and would require little additional infrastructure. Policy adherence and enforcement could be improved with awareness raising with students, faculty and staff. Cessation tools for students must be convenient, understandable, and accessible from multiple locations. Feasible approaches for future initiatives could include testing low cost technology such as quitlines, Web Assisted Tobacco Interventions (WATI) and outside partnerships with community organizations and health agencies