Computational segmentation of collagen fibers from second-harmonic generation images of breast cancer

Bredfeldt, Jeremy S.; Liu, Yuming; Pehlke, Carolyn; Conklin, Matthew W.; Szulczewski, Joseph M.; Inman, David R.; Keely, Patricia J.; Nowak, Robert; Mackie, Thomas Rockwell; Eliceiri, Kevin W.

doi:10.1117/1.jbo.19.1.016007

Cited by 320 publications

(347 citation statements)

References 53 publications

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“…25 CT-FIRE was designed to compute the overall alignment of collagen fibers as well as individual length, straightness, and width. These fiber features were chosen because they appear to be altered in many cancer types compared with normal tissue counterparts.…”

Section: Computational Collagen Fiber Segmentation and Quantificationmentioning

confidence: 99%

Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

et al. 2015

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Pancreatic ductal adenocarcinoma continues to be one of the most difficult diseases to manage with one of the highest cancer mortality rates. This is due to several factors including nonspecific symptomatology and subsequent diagnosis at an advanced stage, aggressive metastatic behavior that is incompletely understood, and limited response to current therapeutic regimens. As in other cancers, there is great interest in studying the role of the tumor microenvironment in pancreatic ductal adenocarcinoma and whether components of this environment could serve as research and therapeutic targets. In particular, attention has turned toward the desmoplastic collagen-rich pancreatic ductal adenocarcinoma stroma for both biological and clinical insight. In this study, we used quantitative second harmonic generation microscopy to investigate stromal collagen organization and structure in human pancreatic ductal adenocarcinoma pathology tissues compared with non-neoplastic tissues. Collagen topology was characterized in whole-tissue microarray cores and at specific pathology-annotated epithelial-stroma interfaces representing 241 and 117 patients, respectively. We quantitatively demonstrate that a unique collagen topology exists in the periductal pancreatic ductal adenocarcinoma stroma. Specifically, collagen around malignant ducts shows increased alignment, length, and width compared with normal ducts and benign ducts in a chronic pancreatitis background. These findings indicate that second harmonic generation imaging can provide quantitative information about fibrosis that complements traditional histopathologic insights and can serve as a rich field for investigation into pathogenic and clinical implications of reorganized collagen as a pancreatic ductal adenocarcinoma disease marker. Pancreatic ductal adenocarcinoma is one of the most devastating human malignancies. It is currently the fourth leading cause of cancer death and projects to become the second leading cause by 2030. 1 The 5-year relative survival rate has remained in the single digits for decades. Pancreatic ductal adenocarcinoma is notoriously difficult to detect before an advanced, inoperable stage is reached due to nonspecific symptomatology and the retroperitoneal location of the pancreas, which makes palpation or routine biopsy of suspicious masses difficult. Recent advances in the sensitivity and specificity of preoperative imaging modalities such as computer tomography, magnetic resonance imaging, positron emission tomography, endoscopic ultrasonography, and endoscopic retrograde cholangiopancreatography have played an important role in enhancing pancreatic ductal adenocarcinoma diagnosis, detailing the relationship of lesions to nearby anatomical structures, and determining the course of management. 2 Despite these advances, only 10-15% of patients are diagnosed at a localized disease stage when surgical resection is possible as a potential curative therapy. However, postsurgical recurrence rates are high with 5-year survival rate of

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Section: Computational Collagen Fiber Segmentation and Quantificationmentioning

confidence: 99%

Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

et al. 2015

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“…In this study, we systematically imaged collagen in tissue regions from 92 pancreatic cancer patients using PSR with a standard polarization widefield microscope followed by subsequent SHG imaging and then quantified collagen properties from both sets of data using well-established software tools for collagen quantification. 29,30 Pancreatic cancer was decided on as a rational cancer model because it remains one of the most deadly human malignancies and has been the subject of recent studies correlating collagen organization to disease progression. 31 In addition, in the context of the tumor microenvironment, an extreme collagen-rich stromal response is a hallmark of pancreatic cancer and can account for up to 90% of the tumor mass.…”

Section: Research-article2016mentioning

confidence: 99%

“…CT-FIRE fiber analysis software 30 (http://loci.wisc.edu/software/ctfire) was then applied to the SHG and PSR-POL images using default settings after thresholding background (20-255 for SHG, 5-255 for PSR-POL). Quantitative information computed by CT-FIRE for each image type included the individual fiber metrics of length, width, and straightness.…”

Section: Fiber Segmentation and Measurementmentioning

confidence: 99%

Comparison of Picrosirius Red Staining With Second Harmonic Generation Imaging for the Quantification of Clinically Relevant Collagen Fiber Features in Histopathology Samples

Drifka

Loeffler

Mathewson

et al. 2016

J Histochem Cytochem.

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SummaryStromal collagen alignment has been shown to have clinical significance in a variety of cancers and in other diseases accompanied by fibrosis. While much of the biological and clinical importance of collagen changes has been demonstrated using second harmonic generation (SHG) imaging in experimental settings, implementation into routine clinical pathology practice is currently prohibitive. To translate the assessment of collagen organization into routine pathology workflow, a surrogate visualization method needs to be examined. The objective of the present study was to quantitatively compare collagen metrics generated from SHG microscopy and commonly available picrosirius red stain with standard polarization microscopy (PSR-POL). Each technique was quantitatively compared with established image segmentation and fiber tracking algorithms using human pancreatic cancer as a model, which is characterized by a pronounced stroma with reorganized collagen fibers. Importantly, PSR-POL produced similar quantitative trends for most collagen metrics in benign and cancerous tissues as measured by SHG. We found it notable that PSR-POL detects higher fiber counts, alignment, length, straightness, and width compared with SHG imaging but still correlates well with SHG results. PSR-POL may provide sufficient and additional information in a conventional clinical pathology laboratory for certain types of collagen quantification. (J Histochem Cytochem 64:519-529, 2016)

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“…Because the tail is threedimensional and angled, for visualization and analyses sum projections of the image z-stacks were generated in FIJI (Schindelin et al, 2012). Sum projections were analyzed for fiber width using CT-FIRE software (Bredfeldt et al, 2014; 2. CT-FIRE | LOCI, available at http://loci.wisc.…”

Section: Shg Imaging and Processingmentioning

confidence: 99%

Matrix metalloproteinase 9 modulates collagen matrices and wound repair

et al. 2015

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Acute and chronic injuries are characterized by leukocyte infiltration into tissues. Although matrix metalloproteinase 9 (Mmp9) has been implicated in both conditions, its role in wound repair remains unclear. We previously reported a zebrafish chronic inflammation mutant caused by an insertion in the hepatocyte growth factor activator inhibitor gene 1 (hai1; also known as spint1) that is characterized by epithelial extrusions and neutrophil infiltration into the fin. Here, we performed a microarray analysis and found increased inflammatory gene expression in the mutant larvae, including a marked increase in mmp9 expression. Depletion of mmp9 partially rescued the chronic inflammation and epithelial phenotypes, in addition to restoring collagen fiber organization, as detected by second-harmonic generation imaging. Additionally, we found that acute wounding induces epithelial cell mmp9 expression and is associated with a thickening of collagen fibers. Interestingly, depletion of mmp9 impaired this collagen fiber reorganization. Moreover, mmp9 depletion impaired tissue regeneration after tail transection, implicating Mmp9 in acute wound repair. Thus, Mmp9 regulates both acute and chronic tissue damage and plays an essential role in collagen reorganization during wound repair.

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Computational segmentation of collagen fibers from second-harmonic generation images of breast cancer

Cited by 320 publications

References 53 publications

Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

Periductal stromal collagen topology of pancreatic ductal adenocarcinoma differs from that of normal and chronic pancreatitis

Comparison of Picrosirius Red Staining With Second Harmonic Generation Imaging for the Quantification of Clinically Relevant Collagen Fiber Features in Histopathology Samples

Matrix metalloproteinase 9 modulates collagen matrices and wound repair

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