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1.
J Pathol Inform ; 15: 100367, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38455864

ABSTRACT

Background: Histological examination of tumor draining lymph nodes (LNs) plays a vital role in cancer staging and prognostication. However, as soon as a LN is classed as metastasis-free, no further investigation will be performed and thus, potentially clinically relevant information detectable in tumor-free LNs is currently not captured. Objective: To systematically study and critically assess methods for the analysis of digitized histological LN images described in published research. Methods: A systematic search was conducted in several public databases up to December 2023 using relevant search terms. Studies using brightfield light microscopy images of hematoxylin and eosin or immunohistochemically stained LN tissue sections aiming to detect and/or segment LNs, their compartments or metastatic tumor using artificial intelligence (AI) were included. Dataset, AI methodology, cancer type, and study objective were compared between articles. Results: A total of 7201 articles were collected and 73 articles remained for detailed analyses after article screening. Of the remaining articles, 86% aimed at LN metastasis identification, 8% aimed at LN compartment segmentation, and remaining focused on LN contouring. Furthermore, 78% of articles used patch classification and 22% used pixel segmentation models for analyses. Five out of six studies (83%) of metastasis-free LNs were performed on publicly unavailable datasets, making quantitative article comparison impossible. Conclusions: Multi-scale models mimicking multiple microscopy zooms show promise for computational LN analysis. Large-scale datasets are needed to establish the clinical relevance of analyzing metastasis-free LN in detail. Further research is needed to identify clinically interpretable metrics for LN compartment characterization.

2.
Med Image Anal ; 93: 103097, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38325154

ABSTRACT

Determining early-stage prognostic markers and stratifying patients for effective treatment are two key challenges for improving outcomes for melanoma patients. Previous studies have used tumour transcriptome data to stratify patients into immune subgroups, which were associated with differential melanoma specific survival and potential predictive biomarkers. However, acquiring transcriptome data is a time-consuming and costly process. Moreover, it is not routinely used in the current clinical workflow. Here, we attempt to overcome this by developing deep learning models to classify gigapixel haematoxylin and eosin (H&E) stained pathology slides, which are well established in clinical workflows, into these immune subgroups. We systematically assess six different multiple instance learning (MIL) frameworks, using five different image resolutions and three different feature extraction methods. We show that pathology-specific self-supervised models using 10x resolution patches generate superior representations for the classification of immune subtypes. In addition, in a primary melanoma dataset, we achieve a mean area under the receiver operating characteristic curve (AUC) of 0.80 for classifying histopathology images into 'high' or 'low immune' subgroups and a mean AUC of 0.82 in an independent TCGA melanoma dataset. Furthermore, we show that these models are able to stratify patients into 'high' and 'low immune' subgroups with significantly different melanoma specific survival outcomes (log rank test, P< 0.005). We anticipate that MIL methods will allow us to find new biomarkers of high importance, act as a tool for clinicians to infer the immune landscape of tumours and stratify patients, without needing to carry out additional expensive genetic tests.


Subject(s)
Melanoma , Humans , Melanoma/diagnostic imaging , Melanoma/genetics , ROC Curve , Staining and Labeling , Workflow , Biomarkers
4.
Gastric Cancer ; 26(6): 847-862, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37776394

ABSTRACT

BACKGROUND: The status of regional tumour draining lymph nodes (LN) is crucial for prognostic evaluation in gastric cancer (GaC) patients. Changes in lymph node microarchitecture, such as follicular hyperplasia (FH), sinus histiocytosis (SH), or paracortical hyperplasia (PH), may be triggered by the anti-tumour immune response. However, the prognostic value of these changes in GaC patients is unclear. METHODS: A systematic search in multiple databases was conducted to identify studies on the prognostic value of microarchitecture changes in regional tumour-negative and tumour-positive LNs measured on histopathological slides. Since the number of GaC publications was very limited, the search was subsequently expanded to include junctional and oesophageal cancer (OeC). RESULTS: A total of 28 articles (17 gastric cancer, 11 oesophageal cancer) met the inclusion criteria, analyzing 26,503 lymph nodes from 3711 GaC and 1912 OeC patients. The studies described eight different types of lymph node microarchitecture changes, categorized into three patterns: hyperplasia (SH, FH, PH), cell-specific infiltration (dendritic cells, T cells, neutrophils, macrophages), and differential gene expression. Meta-analysis of five GaC studies showed a positive association between SH in tumour-negative lymph nodes and better 5-year overall survival. Pooled risk ratios for all LNs showed increased 5-year overall survival for the presence of SH and PH. CONCLUSIONS: This systematic review suggests that sinus histiocytosis and paracortical hyperplasia in regional tumour-negative lymph nodes may provide additional prognostic information for gastric and oesophageal cancer patients. Further studies are needed to better understand the lymph node reaction patterns and explore their impact of chemotherapy treatment and immunotherapy efficacy.


Subject(s)
Esophageal Neoplasms , Histiocytosis, Sinus , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Hyperplasia/pathology , Histiocytosis, Sinus/pathology , Clinical Relevance , Lymph Nodes/surgery , Lymph Nodes/pathology , Prognosis , Esophageal Neoplasms/pathology , Neoplasm Staging
5.
Diagn Pathol ; 18(1): 73, 2023 Jun 12.
Article in English | MEDLINE | ID: mdl-37308870

ABSTRACT

Abdominal aortic aneurysm (AAA) is a pathologic enlargement of the infrarenal aorta with an associated risk of rupture. However, the responsible mechanisms are only partially understood. Based on murine and human samples, a heterogeneous distribution of characteristic pathologic features across the aneurysm circumference is expected. Yet, complete histologic workup of the aneurysm sac is scarcely reported. Here, samples from five AAAs covering the complete circumference partially as aortic rings are investigated by histologic means (HE, EvG, immunohistochemistry) and a new method embedding the complete ring. Additionally, two different methods of serial histologic section alignment are applied to create a 3D view. The typical histopathologic features of AAA, elastic fiber degradation, matrix remodeling with collagen deposition, calcification, inflammatory cell infiltration and thrombus coverage were distributed without recognizable pattern across the aneurysm sac in all five patients. Analysis of digitally scanned entire aortic rings facilitates the visualization of these observations. Immunohistochemistry is feasible in such specimen, however, tricky due to tissue disintegration. 3D image stacks were created using open-source and non-generic software correcting for non-rigid warping between consecutive sections. Secondly, 3D image viewers allowed visualization of in-depth changes of the investigated pathologic hallmarks. In conclusion, this exploratory descriptive study demonstrates a heterogeneous histomorphology around the AAA circumference. Warranting an increased sample size, these results might need to be considered in future mechanistic research, especially in reference to intraluminal thrombus coverage. 3D histology of such circular specimen could be a valuable visualization tool for further analysis.


Subject(s)
Calcinosis , Imaging, Three-Dimensional , Humans , Animals , Mice
6.
Br J Cancer ; 128(12): 2318-2325, 2023 06.
Article in English | MEDLINE | ID: mdl-37029200

ABSTRACT

BACKGROUND: Only a subset of gastric cancer (GC) patients with stage II-III benefits from chemotherapy after surgery. Tumour infiltrating lymphocytes per area (TIL density) has been suggested as a potential predictive biomarker of chemotherapy benefit. METHODS: We quantified TIL density in digital images of haematoxylin-eosin (HE) stained tissue using deep learning in 307 GC patients of the Yonsei Cancer Center (YCC) (193 surgery+adjuvant chemotherapy [S + C], 114 surgery alone [S]) and 629 CLASSIC trial GC patients (325 S + C and 304 S). The relationship between TIL density, disease-free survival (DFS) and clinicopathological variables was analysed. RESULTS: YCC S patients and CLASSIC S patients with high TIL density had longer DFS than S patients with low TIL density (P = 0.007 and P = 0.013, respectively). Furthermore, CLASSIC patients with low TIL density had longer DFS if treated with S + C compared to S (P = 0.003). No significant relationship of TIL density with other clinicopathological variables was found. CONCLUSION: This is the first study to suggest TIL density automatically quantified in routine HE stained tissue sections as a novel, clinically useful biomarker to identify stage II-III GC patients deriving benefit from adjuvant chemotherapy. Validation of our results in a prospective study is warranted.


Subject(s)
Lymphocytes, Tumor-Infiltrating , Stomach Neoplasms , Humans , Biomarkers , Chemotherapy, Adjuvant , Lymphocytes, Tumor-Infiltrating/pathology , Prognosis , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery
7.
Sci Rep ; 13(1): 4774, 2023 03 23.
Article in English | MEDLINE | ID: mdl-36959221

ABSTRACT

The current subjective histopathological assessment of cutaneous melanoma is challenging. The application of image analysis algorithms to histological images may facilitate improvements in workflow and prognostication. To date, several individual algorithms applied to melanoma histological images have been reported with variations in approach and reported accuracies. Histological digital images can be created using a camera mounted on a light microscope, or through whole slide image (WSI) generation using a whole slide scanner. Before any such tool could be integrated into clinical workflow, the accuracy of the technology should be carefully evaluated and summarised. Therefore, the objective of this review was to evaluate the accuracy of existing image analysis algorithms applied to digital histological images of cutaneous melanoma. Database searching of PubMed and Embase from inception to 11th March 2022 was conducted alongside citation checking and examining reports from organisations. All studies reporting accuracy of any image analysis applied to histological images of cutaneous melanoma, were included. The reference standard was any histological assessment of haematoxylin and eosin-stained slides and/or immunohistochemical staining. Citations were independently deduplicated and screened by two review authors and disagreements were resolved through discussion. The data was extracted concerning study demographics; type of image analysis; type of reference standard; conditions included and test statistics to construct 2 × 2 tables. Data was extracted in accordance with our protocol and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Diagnostic Test Accuracy (PRISMA-DTA) Statement. A bivariate random-effects meta-analysis was used to estimate summary sensitivities and specificities with 95% confidence intervals (CI). Assessment of methodological quality was conducted using a tailored version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The primary outcome was the pooled sensitivity and specificity of image analysis applied to cutaneous melanoma histological images. Sixteen studies were included in the systematic review, representing 4,888 specimens. Six studies were included in the meta-analysis. The mean sensitivity and specificity of automated image analysis algorithms applied to melanoma histological images was 90% (CI 82%, 95%) and 92% (CI 79%, 97%), respectively. Based on limited and heterogeneous data, image analysis appears to offer high accuracy when applied to histological images of cutaneous melanoma. However, given the early exploratory nature of these studies, further development work is necessary to improve their performance.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Melanoma/diagnostic imaging , Melanoma/pathology , Sensitivity and Specificity , Algorithms , Melanoma, Cutaneous Malignant
8.
J Pathol Inform ; 14: 100192, 2023.
Article in English | MEDLINE | ID: mdl-36818020

ABSTRACT

Treatment of patients with oesophageal and gastric cancer (OeGC) is guided by disease stage, patient performance status and preferences. Lymph node (LN) status is one of the strongest prognostic factors for OeGC patients. However, survival varies between patients with the same disease stage and LN status. We recently showed that LN size from patients with OeGC might also have prognostic value, thus making delineations of LNs essential for size estimation and the extraction of other imaging biomarkers. We hypothesized that a machine learning workflow is able to: (1) find digital H&E stained slides containing LNs, (2) create a scoring system providing degrees of certainty for the results, and (3) delineate LNs in those images. To train and validate the pipeline, we used 1695 H&E slides from the OE02 trial. The dataset was divided into training (80%) and validation (20%). The model was tested on an external dataset of 826 H&E slides from the OE05 trial. U-Net architecture was used to generate prediction maps from which predefined features were extracted. These features were subsequently used to train an XGBoost model to determine if a region truly contained a LN. With our innovative method, the balanced accuracies of the LN detection were 0.93 on the validation dataset (0.83 on the test dataset) compared to 0.81 (0.81) on the validation (test) datasets when using the standard method of thresholding U-Net predictions to arrive at a binary mask. Our method allowed for the creation of an "uncertain" category, and partly limited false-positive predictions on the external dataset. The mean Dice score was 0.73 (0.60) per-image and 0.66 (0.48) per-LN for the validation (test) datasets. Our pipeline detects images with LNs more accurately than conventional methods, and high-throughput delineation of LNs can facilitate future LN content analyses of large datasets.

9.
J Pathol ; 251(4): 440-451, 2020 08.
Article in English | MEDLINE | ID: mdl-32476144

ABSTRACT

Regular menstrual shedding and repair of the endometrial functionalis is unique to humans and higher-order primates. The current consensus postulates endometrial glands to have a single-tubular architecture, where multi-potential stem cells reside in the blind-ending glandular-bases. Utilising fixed samples from patients, we have studied the three-dimensional (3D) micro-architecture of the human endometrium. We demonstrate that some non-branching, single, vertical functionalis glands originate from a complex horizontally interconnecting network of basalis glands. The existence of a multipotent endometrial epithelial stem cell capable of regenerating the entire complement of glandular lineages was demonstrated by in vivo lineage tracing, using naturally occurring somatic mitochondrial DNA mutations as clonal markers. Vertical tracking of mutated clones showed that at least one stem-cell population resides in the basalis glands. These novel findings provide insight into the efficient and scar-less regenerative potential of the human endometrium. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Subject(s)
Endometrium/ultrastructure , Biomarkers/metabolism , Cell Differentiation , Endometrium/physiology , Female , Humans , Imaging, Three-Dimensional , Menstruation , Stem Cells/physiology , Stem Cells/ultrastructure
10.
Clin Anat ; 33(4): 567-577, 2020 May.
Article in English | MEDLINE | ID: mdl-31385374

ABSTRACT

Intersphincteric resection (ISR) enables radical sphincter-preserving surgery in a subset of low rectal tumors impinging on the anal sphincter complex (ASC). Excellent anatomical knowledge is essential for optimal ISR. This study describes the role of the longitudinal muscle (LM) in the ASC and implications for ISR and other low rectal and anal pathologies. Six human adult en bloc cadaveric specimens (three males, three females) were obtained from the University of Leeds GIFT Research Tissue Programme. Paraffin-embedded mega blocks containing the ASC were produced and serially sectioned at 250 µm intervals. Whole mount microscopic sections were histologically stained and digitally scanned. The intersphincteric plane was shown to be potentially very variable. In some places adipose tissue is located between the external anal sphincter (EAS) and internal anal sphincter (IAS), whereas in others the LM interdigitates to obliterate the plane. Elsewhere the LM is (partly) absent with the intersphincteric plane lying on the IAS. The LM gave rise to the formation of the submucosae and corrugator ani muscles by penetrating the IAS and EAS. In four of six specimens, striated muscle fibers from the EAS curled around the distal IAS reaching the anal submucosa. The ASC formed a complex structure, varying between individuals with an inconstant LM affecting the potential location of the intersphincteric plane as well as a high degree of intermingling striated and smooth muscle fibers potentially further disrupting the plane. The complexity of identifying the correct pathological staging of low rectal cancer is also demonstrated. Clin. Anat. 33:567-577, 2020. © 2019 Wiley Periodicals, Inc.


Subject(s)
Anal Canal/anatomy & histology , Muscle, Smooth/anatomy & histology , Rectal Neoplasms/surgery , Aged , Aged, 80 and over , Cadaver , Female , Humans , Male , Middle Aged
11.
JACC Cardiovasc Imaging ; 11(5): 711-718, 2018 05.
Article in English | MEDLINE | ID: mdl-29747847

ABSTRACT

OBJECTIVES: This study sought to compare the diagnostic accuracy of visual and quantitative analyses of myocardial perfusion cardiovascular magnetic resonance against a reference standard of quantitative coronary angiography. BACKGROUND: Visual analysis of perfusion cardiovascular magnetic resonance studies for assessing myocardial perfusion has been shown to have high diagnostic accuracy for coronary artery disease. However, only a few small studies have assessed the diagnostic accuracy of quantitative myocardial perfusion. METHODS: This retrospective study included 128 patients randomly selected from the CE-MARC (Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease) study population such that the distribution of risk factors and disease status was proportionate to the full population. Visual analysis results of cardiovascular magnetic resonance perfusion images, by consensus of 2 expert readers, were taken from the original study reports. Quantitative myocardial blood flow estimates were obtained using Fermi-constrained deconvolution. The reference standard for myocardial ischemia was a quantitative coronary x-ray angiogram stenosis severity of ≥70% diameter in any coronary artery of >2 mm diameter, or ≥50% in the left main stem. Diagnostic performance was calculated using receiver-operating characteristic curve analysis. RESULTS: The area under the curve for visual analysis was 0.88 (95% confidence interval: 0.81 to 0.95) with a sensitivity of 81.0% (95% confidence interval: 69.1% to 92.8%) and specificity of 86.0% (95% confidence interval: 78.7% to 93.4%). For quantitative stress myocardial blood flow the area under the curve was 0.89 (95% confidence interval: 0.83 to 0.96) with a sensitivity of 87.5% (95% confidence interval: 77.3% to 97.7%) and specificity of 84.5% (95% confidence interval: 76.8% to 92.3%). There was no statistically significant difference between the diagnostic performance of quantitative and visual analyses (p = 0.72). Incorporating rest myocardial blood flow values to generate a myocardial perfusion reserve did not significantly increase the quantitative analysis area under the curve (p = 0.79). CONCLUSIONS: Quantitative perfusion has a high diagnostic accuracy for detecting coronary artery disease but is not superior to visual analysis. The incorporation of rest perfusion imaging does not improve diagnostic accuracy in quantitative perfusion analysis.


Subject(s)
Coronary Circulation , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Myocardial Ischemia/diagnostic imaging , Myocardial Perfusion Imaging/methods , Aged , Coronary Angiography , Female , Humans , Male , Middle Aged , Myocardial Ischemia/physiopathology , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies
12.
Acta Biomater ; 73: 339-354, 2018 06.
Article in English | MEDLINE | ID: mdl-29654989

ABSTRACT

INTRODUCTION: Human ear reconstruction is recognized as the emblematic enterprise in tissue engineering. Up to now, it has failed to reach human applications requiring appropriate tissue complexity along with an accessible vascular tree. We hereby propose a new method to process human auricles in order to provide a poorly immunogenic, complex and vascularized ear graft scaffold. METHODS: 12 human ears with their vascular pedicles were procured. Perfusion-decellularization was applied using a SDS/polar solvent protocol. Cell and antigen removal was examined by histology and DNA was quantified. Preservation of the extracellular matrix (ECM) was assessed by conventional and 3D-histology, proteins and cytokines quantifications. Biocompatibility was assessed by implantation in rats for up to 60 days. Adipose-derived stem cells seeding was conducted on scaffold samples and with human aortic endothelial cells whole graft seeding in a perfusion-bioreactor. RESULTS: Histology confirmed cell and antigen clearance. DNA reduction was 97.3%. ECM structure and composition were preserved. Implanted scaffolds were tolerated in vivo, with acceptable inflammation, remodeling, and anti-donor antibody formation. Seeding experiments demonstrated cell engraftment and viability. CONCLUSIONS: Vascularized and complex auricular scaffolds can be obtained from human source to provide a platform for further functional auricular tissue engineered constructs, hence providing an ideal road to the vascularized composite tissue engineering approach. STATEMENT OF SIGNIFICANCE: The ear is emblematic in the biofabrication of tissues and organs. Current regenerative medicine strategies, with matrix from donor tissues or 3D-printed, didn't reach any application for reconstruction, because critically missing a vascular tree for perfusion and transplantation. We previously described the production of vascularized and cell-compatible scaffolds, from porcine ear grafts. In this study, we ---- applied findings directly to human auricles harvested from postmortem donors, providing a perfusable matrix that retains the ear's original complexity and hosts new viable cells after seeding. This approach unlocks the ability to achieve an auricular tissue engineering approach, associated with possible clinical translation.


Subject(s)
Ear/physiology , Ear/surgery , Extracellular Matrix/chemistry , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Tissue Transplantation/methods , Adipocytes/cytology , Animals , Biocompatible Materials , Bioreactors , Blood Pressure , Cadaver , DNA/analysis , Fluoroscopy , Humans , Leukocytes, Mononuclear/cytology , Perfusion , Rats , Stem Cells/cytology , Stress, Mechanical , Swine
13.
Article in English | MEDLINE | ID: mdl-29392098

ABSTRACT

Myocardial perfusion imaging, coupled with quantitative perfusion analysis, provides an important diagnostic tool for the identification of ischaemic heart disease caused by coronary stenoses. The accurate mapping between coronary anatomy and under-perfused areas of the myocardium is important for diagnosis and treatment. However, in the absence of the actual coronary anatomy during the reporting of perfusion images, areas of ischaemia are allocated to a coronary territory based on a population-derived 17-segment (American Heart Association) AHA model of coronary blood supply. This work presents a solution for the fusion of 2D Magnetic Resonance (MR) myocardial perfusion images and 3D MR angiography data with the aim to improve the detection of ischaemic heart disease. The key contribution of this work is a novel method for the mediated spatiotemporal registration of perfusion and angiography data and a novel method for the calculation of patient-specific coronary supply territories. The registration method uses 4D cardiac MR cine series spanning the complete cardiac cycle in order to overcome the under-constrained nature of non-rigid slice-to-volume perfusion-to-angiography registration. This is achieved by separating out the deformable registration problem and solving it through phase-to-phase registration of the cine series. The use of patient-specific blood supply territories in quantitative perfusion analysis (instead of the population-based model of coronary blood supply) has the potential of increasing the accuracy of perfusion analysis. Quantitative perfusion analysis diagnostic accuracy evaluation with patient-specific territories against the AHA model demonstrates the value of the mediated spatiotemporal registration in the context of ischaemic heart disease diagnosis.

14.
Diagnostics (Basel) ; 8(1)2018 Jan 08.
Article in English | MEDLINE | ID: mdl-29316711

ABSTRACT

AIM: To investigate if the early treatment effects of radiofrequency ablation (RFA) on renal cell carcinoma (RCC) can be detected with dynamic contrast enhanced (DCE)-MRI and to correlate RCC perfusion with RFA treatment time. MATERIALS AND METHODS: 20 patients undergoing RFA of their 21 RCCs were evaluated with DCE-MRI before and at one month after RFA treatment. Perfusion was estimated using the maximum slope technique at two independent sittings. Total RCC blood flow was correlated with total RFA treatment time, tumour location, size and histology. RESULTS: DCE-MRI examinations were successfully evaluated for 21 RCCs (size from 1.3 to 4 cm). Perfusion of the RCCs decreased significantly (p < 0.0001) from a mean of 203 (±80) mL/min/100 mL before RFA to 8.1 (±3.1) mL/min/100 mL after RFA with low intra-observer variability (r ≥ 0.99, p < 0.0001). There was an excellent correlation (r = 0.95) between time to complete ablation and pre-treatment total RCC blood flow. Tumours with an exophytic location exhibit the lowest mean RFA treatment time. CONCLUSION: DCE-MRI can detect early treatment effects by measuring RCC perfusion before and after RFA. Perfusion significantly decreases in the zone of ablation, suggesting that it may be useful for the assessment of treatment efficacy. Pre-RFA RCC blood flow may be used to predict RFA treatment time.

15.
J Oral Pathol Med ; 47(1): 53-59, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28960470

ABSTRACT

OBJECTIVES: Margin status and invasion pattern are prognostic factors for oral tongue squamous cell carcinoma (OTSCC). Current methods to identify these factors are limited to 2D observation; it is necessary to explore 3D reconstruction with whole-mount sample to improve the accuracy of analysis. This study aimed to study the tissue preparation, section generation, and 3D reconstruction with whole-mount OTSCC specimen. STUDY DESIGN: Two OTSCC samples were retrieved from Nanjing Stomatological Hospital, Medical School of Nanjing University. One sample was sliced into 3 equal-sized pieces and subjected to different processing schedules to determine the best method. The second sample was processed accordingly. Serial whole-mount sections of the second sample were generated, stained with HE/anticytokine antibody in intersection manner, and scanned into digital images. Digital images were aligned and reconstructed into 3D images with Hetero Genius Medical Image Manager 3D Pathology Add-On [HGMIM3D]. RESULTS: Successful serial whole-mount sections of comparable quality to traditional sections were generated. Three-dimensional images with serial whole-mount sections were successfully generated. CONCLUSIONS: Whole-mount histopathological 3D reconstruction of OTSCC was successfully generated, providing a solid foundation for comprehensive margin and invasion analysis. Although future study and improvement were needed, whole-mount histopathological 3D reconstruction proved to be a promising method in OTSCC study.


Subject(s)
Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/pathology , Histological Techniques/methods , Imaging, Three-Dimensional/methods , Tongue Neoplasms/diagnostic imaging , Tongue Neoplasms/pathology , Histological Techniques/instrumentation , Humans , Image Processing, Computer-Assisted/instrumentation , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/instrumentation , Squamous Cell Carcinoma of Head and Neck , Staining and Labeling
16.
Magn Reson Med ; 78(1): 285-296, 2017 07.
Article in English | MEDLINE | ID: mdl-27510300

ABSTRACT

PURPOSE: The aim of this work was to quantify the extent of lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques. METHODS: Patients scheduled for carotid endarterectomy underwent four-point Dixon and T1-weighted magnetic resonance imaging (MRI) at 3 Tesla. Fat and R2* maps were generated from the Dixon sequence at the acquired spatial resolution of 0.60 × 0.60 × 0.70 mm voxel size. MRI and three-dimensional (3D) histology volumes of plaques were registered. The registration matrix was applied to segmentations denoting LRNC and IPH in 3D histology to split plaque volumes in regions with and without LRNC and IPH. RESULTS: Five patients were included. Regarding volumes of LRNC identified by 3D histology, the average fat fraction by MRI was significantly higher inside LRNC than outside: 12.64 ± 0.2737% versus 9.294 ± 0.1762% (mean ± standard error of the mean [SEM]; P < 0.001). The same was true for IPH identified by 3D histology, R2* inside versus outside IPH was: 71.81 ± 1.276 s-1 versus 56.94 ± 0.9095 s-1 (mean ± SEM; P < 0.001). There was a strong correlation between the cumulative fat and the volume of LRNC from 3D histology (R2 = 0.92) as well as between cumulative R2* and IPH (R2 = 0.94). CONCLUSION: Quantitative mapping of fat and R2* from Dixon MRI reliably quantifies the extent of LRNC and IPH. Magn Reson Med 78:285-296, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Subject(s)
Adipose Tissue/metabolism , Adipose Tissue/pathology , Carotid Artery Diseases/metabolism , Carotid Artery Diseases/pathology , Hemorrhage/metabolism , Hemorrhage/pathology , Magnetic Resonance Imaging/methods , Adipose Tissue/diagnostic imaging , Aged , Aged, 80 and over , Biomarkers/metabolism , Carotid Artery Diseases/diagnostic imaging , Hemorrhage/diagnostic imaging , Humans , Image Interpretation, Computer-Assisted/methods , Lipid Metabolism , Male , Middle Aged , Models, Biological , Models, Statistical , Molecular Imaging/methods , Necrosis/diagnostic imaging , Necrosis/metabolism , Necrosis/pathology , Reproducibility of Results , Sensitivity and Specificity , Signal Processing, Computer-Assisted
17.
Sensors (Basel) ; 16(11)2016 Nov 02.
Article in English | MEDLINE | ID: mdl-27827836

ABSTRACT

We address the problem of accurately locating buried utility segments by fusing data from multiple sensors using a novel Marching-Cross-Section (MCS) algorithm. Five types of sensors are used in this work: Ground Penetrating Radar (GPR), Passive Magnetic Fields (PMF), Magnetic Gradiometer (MG), Low Frequency Electromagnetic Fields (LFEM) and Vibro-Acoustics (VA). As part of the MCS algorithm, a novel formulation of the extended Kalman Filter (EKF) is proposed for marching existing utility tracks from a scan cross-section (scs) to the next one; novel rules for initializing utilities based on hypothesized detections on the first scs and for associating predicted utility tracks with hypothesized detections in the following scss are introduced. Algorithms are proposed for generating virtual scan lines based on given hypothesized detections when different sensors do not share common scan lines, or when only the coordinates of the hypothesized detections are provided without any information of the actual survey scan lines. The performance of the proposed system is evaluated with both synthetic data and real data. The experimental results in this work demonstrate that the proposed MCS algorithm can locate multiple buried utility segments simultaneously, including both straight and curved utilities, and can separate intersecting segments. By using the probabilities of a hypothesized detection being a pipe or a cable together with its 3D coordinates, the MCS algorithm is able to discriminate a pipe and a cable close to each other. The MCS algorithm can be used for both post- and on-site processing. When it is used on site, the detected tracks on the current scs can help to determine the location and direction of the next scan line. The proposed "multi-utility multi-sensor" system has no limit to the number of buried utilities or the number of sensors, and the more sensor data used, the more buried utility segments can be detected with more accurate location and orientation.

19.
J Med Imaging (Bellingham) ; 3(2): 024002, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27213166

ABSTRACT

Respiratory motion is a significant obstacle to the use of quantitative perfusion in clinical practice. Increasingly complex motion correction algorithms are being developed to correct for respiratory motion. However, the impact of these improvements on the final diagnosis of ischemic heart disease has not been evaluated. The aim of this study was to compare the performance of four automated correction methods in terms of their impact on diagnostic accuracy. Three strategies for motion correction were used: (1) independent translation correction for all slices, (2) translation correction for the basal slice with transform propagation to the remaining two slices assuming identical motion in the remaining slices, and (3) rigid correction (translation and rotation) for the basal slice. There were no significant differences in diagnostic accuracy between the manual and automatic motion-corrected datasets ([Formula: see text]). The area under the curve values for manual motion correction and automatic motion correction were 0.93 and 0.92, respectively. All of the automated motion correction methods achieved a comparable diagnostic accuracy to manual correction. This suggests that the simplest automated motion correction method (method 2 with translation transform for basal location and transform propagation to the remaining slices) is a sufficiently complex motion correction method for use in quantitative myocardial perfusion.

20.
Biomed Opt Express ; 7(5): 2022-35, 2016 May 01.
Article in English | MEDLINE | ID: mdl-27231640

ABSTRACT

Raman spectroscopy was used to differentiate between mucosally healed (or quiescent) and inflamed colon tissue, as assessed endoscopically, in patients with ulcerative colitis. From the analysis of the Raman spectra of 60 biopsy tissue samples, clear differences were identified between the spectra of the quiescent and inflamed tissue. Three carotenoid peaks were found to be approximately twice as intense in the inflamed tissue. Two phospholipid peaks were found to be significantly lower in the inflamed tissue. Using multivariate statistical analysis, we show that these five peaks can be used to discriminate between endoscopically quiescent and inflamed tissue. We also correlated the Raman data with a histological assessment of the tissue. Four of the five peaks were found to be significantly different between the spectra of histologically healed (or quiescent) and histologically inflamed tissue. These findings indicate the ability of Raman spectroscopy to accurately classify colon tissue as either quiescent or inflamed, irrespective of whether an endoscopic or histological grading scheme is followed. We thus demonstrate that Raman spectroscopy could potentially be used as an early diagnosis tool for assessing the presence of mucosal healing or inflammation in patients with ulcerative colitis.

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