REVIEW ARTICLE
Year : 2014  |  Volume : 18  |  Issue : 4  |  Page : 111-116

Artefacts in histopathology

Shailja Chatterjee
Department of Oral and Maxillofacial Pathology, MM College of Dental Sciences and Research, Maharishi Markandeshwar University, Mullana, Haryana, India

Correspondence Address:
Shailja Chatterjee
Deparment of Oral and Maxillofacial Pathology, MM College of Dental Sciences and Research, Maharishi Markandeshwar University, Mullana - 133 207, Haryana
India

Source of Support: None, Conflict of Interest: None

Check

58

DOI: 10.4103/0973-029X.141346

Abstract

Histopathology is the science of slide analysis for the diagnostic and research purposes. However, sometimes the presence of certain artefacts in a microscopic section can result in misinterpretations leading to diagnostic pitfalls that can result in increased patient morbidity. This article reviews the common artefacts encountered during slide examination alongside the remedial measures which can be undertaken to differentiate between an artefact and tissue constituent.

Keywords: Artefacts, diagnostic pitfalls, histopathology, morbidity, mortality, remedies

Introduction

Causes of artefacts

1. Clinical application of chemicals
2. Local injection of anesthetics
3. Surgical suctioning
4. Excessive heat
5. Freezing
6. Surgical mishandling of specimen
7. Inadequate tissue fixation
8. Improper fixation medium
9. Faulty tissue processing
10. Embedded sponges
11. Improper staining.

Classification of Artefacts

1. During surgery
   1. Injection artefacts
   2. Forceps artefacts
   3. Fulguration artefacts.
2. During fixation and transport
   1. Fixation artefacts
   2. Freezing artefacts
   3. Artefacts during transportation.
3. Tissue processing artefacts
4. Other artefacts
   1. During Surgery.

1. Needle insertion may produce hemorrhage with extravasation that masks the cellular architecture
2. Separation of connective tissue bands with vacuolization can occur.

Remedy

Remedy

1. Use small atraumatic forceps or Adson's forceps without teeth
2. A suture should be placed in one edge of the specimen (substitute for forceps for tissue immobilization).

Remedy

1. The use of electrocautery is contra-indicated as biopsy technique for it is deleterious to interpretation of the tissue although it is desirable for surgery because it aids hemostasis
2. Care must be exercised to use the cutting and not the coagulation electrode when obtaining a biopsy specimen so that low milliampere current will be produced that will allow efficient cutting and liberation of specimen
3. The incision margin should be adequaltely away from the interface of the lesion with normal tissue to prevent thermal changes
4. One should avoid accidental contact of cutting tip with the metallic instrument used for holding the specimen
5. Scalpel should be used for initial incision around or into the lesion to be biopsied and followed by electrosurgery to complete the removal of tissue.

1. Artefacts related to diffusion of unfixed material: Diffusion of unfixed material may produce false localization due to movement to some place other than its original location. For example, false localization occurring with glycogen is known as streaming artefact
2. Diffusion of materials out of tissue: Examples include inorganic ions, cofactors for enzymes, biogenic amines. These have implications in techniques like enzyme histochemistry
3. False fixation of extraneous material to tissue: This may occur in autoradiography with (H ³ ) labeled amino acids, sugars, thymidine and uridine. Tissues may incorporate these substances into themselves by active metabolism resulting in too high localization of various radioactively labeled substances
4. Improper Fixation: Delay in fixation or inadequate fixation produces changes like [Figure 1]:
   1. Altered staining quality of cells
   2. Cells appear shrunken and show cytoplasmic clumping
   3. Indistinct nuclear chromatin with nucleoli sometimes not seen
   4. Vascular structures, nerves and glands exhibit loss of detail
   5. Impression of scar formation or loss of cellularity
   6. Use of improper fixative: Fixation in alcohol results in poor staining of the epithelium and improper fixation of the connective tissue. Collagen bundles have an amorphous appearance that is not a result of scar formation but rather result of artefact. Alcohol fixes tissues but causes severe shrinkage. Therefore, alcohol is not recommended as a substitute for formalin except in extreme emergencies. It also makes the tissue brittle, resulting in microtome sectioning artefacts with chattering and a Venetian blind appearance [Figure 2] and [Figure 3]. Currently, 10% neutral buffered formalin is highly recommended for routine fixation purposes. One excellent indicator of poor fixation is the loss of detail of extravasated RBC's.

Figure 1: Photomicrograph showing tissue autolysis due to improper fixation (×10) Click here to view

Figure 2: Photomicrograph showing folding of section (×10) Click here to view

Figure 3: Photomicrograph showing contamination by spores (×10) Click here to view

1. Use of Lillie's acetic acid, alcohol, formalin (AAF): A fixative containing 40% formaldehyde: 10 parts; glacial acetic acid: 15 parts and absolute ethyl alcohol: 85 parts. This solution's freezing point is below -30°C (-22°F).The preservation of morphological details compares favorably with that of tissue fixed in 10% formalin. ^[3]
2. Acetic acid causes cellular constituents to swell, thereby, counteracting the adverse effects of alcohol. However, it causes good nuclear preservation.

1. When a biopsy is handled in the laboratory, it may become adulterated with small fragments of other tissues being processed in the same batch
2. When the tissue sections are being floated out on a water bath they may pick up residual fragments of other sections previously floated out on same water bath. ^[6] Floater artefact may be suspected if ^[6]
   1. A tissue fragment looks different from others by virtue of section thickness and/or staining intensity
   2. A tissue fragment is on a slightly different plane from others, especially if superimposed
   3. A tissue fragment showing pathologic changes totally different from others and of a type that one would not have expected at all under the clinical circumstances of the particular case.

1. Most common artefact of this type is "shrinkage". This may be due to dehydration by alcohol. All types of tissue components may appear smaller than they are and clear spaces may appear around such cells and between tissues
2. Loss of fat: Fat containing cells appear "empty".

1. Stain Particles: Incorporation of stain particles occurs when staining chemicals are not dissolved properly or the stain is not fresh, leading to precipitation. Remedy: Filter the stain
2. Air Bubbles: These get trapped when cover slip is placed over stained section. These appear as tiny spherical features.

1. Use adequate amount of mounting media
2. If the mounting media has attained greater viscosity, xylene can be used as a thinning agent.

1. Folds in sections: Sometimes wrinkles on the wax sections cannot be straightened resulting in folds or pleats. This is a common artefact in tissues with hard tissue component and is difficult to avoid even with greatest care
2. Cloudy appearance of sections: Faulty dehydration technique results in cloudiness in sections. Remedy: Rehydrate the tissue section and repeat the processing
3. Dirt or Dust: Usually the dirt on the slides is "out of focus" when the section is in sharp focus because the cover slip thickness separates the two
4. Foreign bodies including starch from glove powder entrapped in fibrin and wood fragments from the surface on which tissue is handled and dissected. It is easy to identify these particles of foreign material as artefactual because there will be no associated tissue reaction like foreign body giant cells.

1. Formalin Pigment: Acid formaldehyde hematin is formed in the tissues by the action of acid formaldehyde solution on hemoglobin. It is therefore found in association with blood and is most commonly seen in spleen, liver, lung, bone marrow and in association with areas of hemorrhage and blood vessels. The pigment appears dark brown in color and is composed of small birefringent crystals. Remedy: Formation of pigment can be limited by fixing in non-acid formaldehyde. For example, neutral buffered formalin. However, formation of formalin pigment is not always prevented by the use of buffered formalin especially, prolonged fixation. Formalin pigment may be removed by treating the section with alcoholic ammonia or alcoholic sodium or potassium hydroxide. These methods, however, have the tendency of removing the sections from the slide. Therefore, the method of choice is use of saturated alcoholic solution of picric acid before the staining procedure. The time required for removal varies from 15 minutes to overnight. Malarial and bilharzial pigments are similar to formalin pigment in all their reactions but may be differentiated from the latter by their intracellular distribution
2. Mercury pigment: Tissues fixed in solutions containing mercuric chloride contain a varying amount of a dark brown or grey deposit of granules or irregular masses. The deposits are found throughout the tissue. Remedy: It is easily removed from the section by oxidation with iodine to mercuric iodide which can be subsequently removed with sodium thiosulfate
3. Chromate Deposits: If tissues are not thoroughly washed in water after fixation in chromate-containing fixatives, the chrome salts will react with the dehydrating alcohol forming a yellow-brown to black precipitate within the tissue. Remedy: This can be removed by treating the section for at least 30 minutes with 1% HCl in 70% alcohol.
4. Stain Deposits: They may be amorphous or crystalline in appearance and are usually highly colored. They are most likely to occur if concentrated solutions are allowed to evaporate on the sections. Remedy: Surface layers of precipitated stain are removed from the staining bath by filtration otherwise the precipitate will be deposited on the surface of section as it is withdrawn from the staining bath.
   • Paraffin Wax: Wax is sometimes retained in the section, particularly in nuclei. It can be clearly recognized by its position, refractile appearance and its birefringence. Remedy: It can be removed by treating the section in xylene at 60°C.

References

1.	Margarone JE, Natiella JR, Vaughan CD. Artefacts in oral biopsy specimens. J Oral Maxillofac Surg 1985;43:163-72.   [PUBMED]
2.	Ficarra G, McClintock B, Hansen LS. Artefacts created during oral biopsy procedures. J Craniomaxillofac Surg 1987;15:34-7.   [PUBMED]
3.	Okun MR, Ellerin P, Piotrowicz MA. Prevention of ice crystal damage to biopsy specimens in transport. Arch Dermatol 1972;105:458-9.   [PUBMED]
4.	Kepes JJ, Oswald O. Tissue artefacts caused by sponge in embedded cassettes. Am J Surg Pathol 1991;15:810-2.
5.	Farell DJ, Thompson PJ, Morley AR. Tissue artefacts caused by sponges. J Clin Pathol 1992;45:923-4.
6.	McInnes E. Artefacts in histopathology. Comp Clin Path 2005;13:100-8.
7.	Culing CF, Allison RT, Barr WT. Culling CA in microtome and microtomy. Cellular Pathology Techniques. 4 th ed. Oxford university press.

This article has been cited by 1 Effect of squalane-based emulsion on polyphenols skin penetration: Ex vivo skin study Ana L.S. Oliveira, Diana Valente, Helena R. Moreira, Manuela Pintado, Patrícia Costa Colloids and Surfaces B: Biointerfaces. 2022; 218: 112779 [Pubmed] | [DOI] 2 Pathologists’ perspective on the study design, analysis, and interpretation of proliferative lesions in lifetime and prenatal rodent carcinogenicity bioassays of aspartame Susan A. Elmore, Jerold E. Rehg, Trenton R. Schoeb, Jeffrey I. Everitt, Brad Bolon Food and Chemical Toxicology. 2022; : 113504 [Pubmed] | [DOI] 3 Deep learning enables ultraviolet photoacoustic microscopy based histological imaging with near real-time virtual staining Lei Kang, Xiufeng Li, Yan Zhang, Terence T.W. Wong Photoacoustics. 2022; 25: 100308 [Pubmed] | [DOI] 4 Recommendations on compiling test datasets for evaluating artificial intelligence solutions in pathology André Homeyer, Christian Geißler, Lars Ole Schwen, Falk Zakrzewski, Theodore Evans, Klaus Strohmenger, Max Westphal, Roman David Bülow, Michaela Kargl, Aray Karjauv, Isidre Munné-Bertran, Carl Orge Retzlaff, Adrià Romero-López, Tomasz Soltysinski, Markus Plass, Rita Carvalho, Peter Steinbach, Yu-Chia Lan, Nassim Bouteldja, David Haber, Mateo Rojas-Carulla, Alireza Vafaei Sadr, Matthias Kraft, Daniel Krüger, Rutger Fick, Tobias Lang, Peter Boor, Heimo Müller, Peter Hufnagl, Norman Zerbe Modern Pathology. 2022; [Pubmed] | [DOI] 5 Elucidating tumor heterogeneity from spatially resolved transcriptomics data by multi-view graph collaborative learning Chunman Zuo, Yijian Zhang, Chen Cao, Jinwang Feng, Mingqi Jiao, Luonan Chen Nature Communications. 2022; 13(1) [Pubmed] | [DOI] 6 Morphometric analysis of the human common hepatic artery reveals a rich and accessible target for sympathetic liver denervation Abraham Rami Tzafriri, Fernando Garcia-Polite, John Keating, Raffaele Melidone, Jennifer Knutson, Peter Markham, Elazer R. Edelman, Felix Mahfoud Scientific Reports. 2022; 12(1) [Pubmed] | [DOI] 7 Self-supervised learning of cell type specificity from immunohistochemical images Michael Murphy, Stefanie Jegelka, Ernest Fraenkel Bioinformatics. 2022; 38(Supplement): i395 [Pubmed] | [DOI] 8 Nrf2 activation in the human brain after stroke due to supratentorial intracerebral haemorrhage: a case–control study Edward Christopher, James J M Loan, Neshika Samarasekera, Karina McDade, Jamie Rose, Jack Barrington, Jeremy Hughes, Colin Smith, Rustam Al-Shahi Salman BMJ Neurology Open. 2022; 4(1): e000238 [Pubmed] | [DOI] 9 Scientific and Regulatory Policy Committee Points to Consider for Medical Device Implant Site Evaluation in Nonclinical Studies Maureen T. O’Brien, JoAnn C. L. Schuh, Lyn M. Wancket, Sarah D. Cramer, Kathleen A. Funk, Nicolette D. Jackson, Kamala Kannan, Kevin Keane, Abraham Nyska, Serge D. Rousselle, Adrienne Schucker, Valerie S. Thomas, Stefan Tunev Toxicologic Pathology. 2022; : 0192623322 [Pubmed] | [DOI] 10 Introduction of In Vivo Confocal Laser Endomicroscopy and Real-Time Telepathology for Remote Intraoperative Neurosurgery-Pathology Consultation Marian T. Park, Irakliy Abramov, Timothy C. Gooldy, Kris A. Smith, Randall W. Porter, Andrew S. Little, Michael T. Lawton, Jennifer M. Eschbacher, Mark C. Preul Operative Neurosurgery. 2022; 23(3): 261 [Pubmed] | [DOI] 11 Real-time intraoperative surgical telepathology using confocal laser endomicroscopy Irakliy Abramov, Marian T. Park, Timothy C. Gooldy, Yuan Xu, Michael T. Lawton, Andrew S. Little, Randall W. Porter, Kris A. Smith, Jennifer M. Eschbacher, Mark C. Preul Neurosurgical Focus. 2022; 52(6): E9 [Pubmed] | [DOI] 12 Reversible contrast enhancement for visualization of human temporal bones using micro computed tomography Krishna K. Bommakanti, Janani S. Iyer, Varun Sagi, Alyssa Brown, Xiaojie Ma, Marissa Gonzales, Konstantina M. Stankovic Frontiers in Surgery. 2022; 9 [Pubmed] | [DOI] 13 Assessment of knowledge, attitude, and practice of tissue preservation among dentists practicing at Navi Mumbai and Mumbai Kirti Buva, Bhavana Bharambe, Ajinkya Deshmukh, Atul Deshmukh, Dhrtika Bhatia, Shreya Hiwalkar, Deepak M. Vikhe International journal of health sciences. 2022; : 4943 [Pubmed] | [DOI] 14 Biliary Microhamartoma in a Patient with Esophagogastric Junction Cancer That Resembled a Metastatic Liver Tumor and Significantly Influenced the Surgical Indication: Report of a Case Yuki Shimada, Kenoki Ohuchida, Takashi Matsumoto, Koji Shindo, Taiki Moriyama, Yusuke Mizuuchi, Kohei Nakata, Takeo Yamamoto, Mikiko Hashisako, Yoshinao Oda, Masafumi Nakamura The Japanese Journal of Gastroenterological Surgery. 2022; 55(5): 311 [Pubmed] | [DOI] 15 Stress testing pathology models with generated artifacts NicholasChandler Wang, Jeremy Kaplan, Joonsang Lee, Jeffrey Hodgin, Aaron Udager, Arvind Rao Journal of Pathology Informatics. 2021; 12(1): 54 [Pubmed] | [DOI] 16 Prevalence of Duodenum Brunner Gland Crush Artifact: A Retrospective Study Murat ÇELIK Ahi Evran Medical Journal. 2021; [Pubmed] | [DOI] 17 Artefacts in Volume Data Generated with High Resolution Episcopic Microscopy (HREM) Lukas F. Reissig, Stefan H. Geyer, Julia Rose, Fabrice Prin, Robert Wilson, Dorota Szumska, Antonella Galli, Catherine Tudor, Jacqueline K. White, Tim J. Mohun, Wolfgang J. Weninger Biomedicines. 2021; 9(11): 1711 [Pubmed] | [DOI] 18 Fluorescence Microscopy—An Outline of Hardware, Biological Handling, and Fluorophore Considerations Shane M. Hickey, Ben Ung, Christie Bader, Robert Brooks, Joanna Lazniewska, Ian R. D. Johnson, Alexandra Sorvina, Jessica Logan, Carmela Martini, Courtney R. Moore, Litsa Karageorgos, Martin J. Sweetman, Douglas A. Brooks Cells. 2021; 11(1): 35 [Pubmed] | [DOI] 19 A Review of Ex Vivo X-ray Microfocus Computed Tomography-Based Characterization of the Cardiovascular System Lisa Leyssens, Camille Pestiaux, Greet Kerckhofs International Journal of Molecular Sciences. 2021; 22(6): 3263 [Pubmed] | [DOI] 20 Confocal Laser Microscopy in Neurosurgery: State of the Art of Actual Clinical Applications Francesco Restelli, Bianca Pollo, Ignazio Gaspare Vetrano, Samuele Cabras, Morgan Broggi, Marco Schiariti, Jacopo Falco, Camilla de Laurentis, Gabriella Raccuia, Paolo Ferroli, Francesco Acerbi Journal of Clinical Medicine. 2021; 10(9): 2035 [Pubmed] | [DOI] 21 Detecting Borrelia Spirochetes: A Case Study With Validation Among Autopsy Specimens Shiva Kumar Goud Gadila, Gorazd Rosoklija, Andrew J. Dwork, Brian A. Fallon, Monica E. Embers Frontiers in Neurology. 2021; 12 [Pubmed] | [DOI] 22 Developing a Qualification and Verification Strategy for Digital Tissue Image Analysis in Toxicological Pathology Aleksandra Zuraw, Michael Staup, Robert Klopfleisch, Famke Aeffner, Danielle Brown, Thomas Westerling-Bui, Daniel Rudmann Toxicologic Pathology. 2021; 49(4): 773 [Pubmed] | [DOI] 23 Accuracy of cone-beam computed tomography for the evaluation of mandible invasion by oral squamous cell carcinoma Zezheng Wang, Shuang Zhang, Yumei Pu, Yuxin Wang, Zitong Lin, Zhiyong Wang BMC Oral Health. 2021; 21(1) [Pubmed] | [DOI] 24 Comparing Needles and Methods of Endoscopic Ultrasound–Guided Fine-Needle Biopsy to Optimize Specimen Quality and Diagnostic Accuracy for Patients With Pancreatic Masses in a Randomized Trial Ji Young Bang, Konrad Krall, Nirag Jhala, Charanjeet Singh, Mohamedtaki Tejani, Juan Pablo Arnoletti, Udayakumar Navaneethan, Robert Hawes, Shyam Varadarajulu Clinical Gastroenterology and Hepatology. 2021; 19(4): 825 [Pubmed] | [DOI] 25 Extreme winter weather: A force to be remembered in dermatopathology Katie Dreher, Angela Zaladonis, Rodrigo Valdes-Rodriguez Journal of Cutaneous Pathology. 2021; 48(9): 1204 [Pubmed] | [DOI] 26 Kidney Level Lupus Nephritis Classification Using Uncertainty Guided Bayesian Convolutional Neural Networks Pietro Antonio Cicalese, Aryan Mobiny, Zahed Shahmoradi, Xiongfeng Yi, Chandra Mohan, Hien Van Nguyen IEEE Journal of Biomedical and Health Informatics. 2021; 25(2): 315 [Pubmed] | [DOI] 27 Processing and Analysis of Tissue Samples from Esophageal Cancer Patients in an African Setting Lucien Ferndale, Mishalan Moodley, Wenlong C. Chen, Reubina Wadee, Colleen A. Wright, Mohamed Iqbal Parker, Pascale Willem, Christopher G. Mathew Biopreservation and Biobanking. 2021; [Pubmed] | [DOI] 28 The impact of site-specific digital histology signatures on deep learning model accuracy and bias Frederick M. Howard, James Dolezal, Sara Kochanny, Jefree Schulte, Heather Chen, Lara Heij, Dezheng Huo, Rita Nanda, Olufunmilayo I. Olopade, Jakob N. Kather, Nicole Cipriani, Robert L. Grossman, Alexander T. Pearson Nature Communications. 2021; 12(1) [Pubmed] | [DOI] 29 Pay attention to doctor–patient dialogues: Multi-modal knowledge graph attention image-text embedding for COVID-19 diagnosis Wenbo Zheng, Lan Yan, Chao Gou, Zhi-Cheng Zhang, Jun Jason Zhang, Ming Hu, Fei-Yue Wang Information Fusion. 2021; 75: 168 [Pubmed] | [DOI] 30 Comparative analysis of CT guided vertebral biopsy by a conventional bone biopsy needle versus bone biopsy needle with acquisition cradle Dharmendra Kumar Singh, Tankeshwar Boruah, Anuradha Sharma, Geetika Khanna, Loveneesh G. Krishna, Nishith Kumar Journal of Clinical Orthopaedics and Trauma. 2021; 19: 231 [Pubmed] | [DOI] 31 Statistical and machine learning methods for spatially resolved transcriptomics with histology Jian Hu, Amelia Schroeder, Kyle Coleman, Chixiang Chen, Benjamin J. Auerbach, Mingyao Li Computational and Structural Biotechnology Journal. 2021; 19: 3829 [Pubmed] | [DOI] 32 Deep Learning for Clinical Image Analyses in Oral Squamous Cell Carcinoma Chui Shan Chu, Nikki P. Lee, Joshua W. K. Ho, Siu-Wai Choi, Peter J. Thomson JAMA Otolaryngology–Head & Neck Surgery. 2021; 147(10): 893 [Pubmed] | [DOI] 33 Diagnostic concordance between ultrasound-guided core needle biopsy and surgical resection specimens for histological grading of extremity and trunk soft tissue sarcoma A. Tan, R. Rajakulasingam, A. Saifuddin Skeletal Radiology. 2021; 50(1): 43 [Pubmed] | [DOI] 34 Histological Validation of MRI: A Review of Challenges in Registration of Imaging and Whole-Mount Histopathology Wadha Alyami, Andre Kyme, Roger Bourne Journal of Magnetic Resonance Imaging. 2020; [Pubmed] | [DOI] 35 Spatially-directed cell migration in acoustically-responsive scaffolds through the controlled delivery of basic fibroblast growth factor Xiaofang Lu, Hai Jin, Carole Quesada, Easton C. Farrell, Leidan Huang, Mitra Aliabouzar, Oliver D. Kripfgans, J. Brian Fowlkes, Renny T. Franceschi, Andrew J. Putnam, Mario L. Fabiilli Acta Biomaterialia. 2020; 113: 217 [Pubmed] | [DOI] 36 MicroCT optimisation for imaging fascicular anatomy in peripheral nerves Nicole Thompson, Enrico Ravagli, Svetlana Mastitskaya, Francesco Iacoviello, Kirill Aristovich, Justin Perkins, Paul R Shearing, David Holder Journal of Neuroscience Methods. 2020; 338: 108652 [Pubmed] | [DOI] 37 Histomorphological assessment of isolated abdominal organs after targeted perfusion with the contrast agent Angiofil® in postmortem computed tomography angiography Christian Jean-Paul Stumm, Holger Wittig, Nicole M. Kalberer, Eva Scheurer Forensic Science International. 2020; 315: 110427 [Pubmed] | [DOI] 38 Utero-placental vascular remodeling during late gestation in Sprague-Dawley rats Frank T. Spradley, Ying Ge, Joey P. Granger, Alejandro R. Chade Pregnancy Hypertension. 2020; 20: 36 [Pubmed] | [DOI] 39 Geometry influences inflammatory host cell response and remodeling in tissue-engineered heart valves in-vivo Sarah E. Motta, Emanuela S. Fioretta, Valentina Lintas, Petra E. Dijkman, Monika Hilbe, Laura Frese, Nikola Cesarovic, Sandra Loerakker, Frank P. T. Baaijens, Volkmar Falk, Simon P. Hoerstrup, Maximilian Y. Emmert Scientific Reports. 2020; 10(1) [Pubmed] | [DOI] 40 Revealing the Microscopic Structure of Human Renal Cell Carcinoma in Three Dimensions S. Ferstl, M. Busse, M. Muller, M. A. Kimm, E. Drecoll, T. Burkner, S. Allner, M. Dierolf, D. Pfeiffer, E. J. Rummeny, W. Weichert, F. Pfeiffer IEEE Transactions on Medical Imaging. 2020; 39(5): 1494 [Pubmed] | [DOI] 41 Multiscale modelling of drug transport and metabolism in liver spheroids Joseph A. Leedale, Jonathan A. Kyffin, Amy L. Harding, Helen E. Colley, Craig Murdoch, Parveen Sharma, Dominic P. Williams, Steven D. Webb, Rachel N. Bearon Interface Focus. 2020; 10(2): 20190041 [Pubmed] | [DOI] 42 Bimodal Whole-Mount Imaging of Tendon Using Confocal Microscopy and X-ray Micro-Computed Tomography Neil Marr, Mark Hopkinson, Andrew P. Hibbert, Andrew A. Pitsillides, Chavaunne T. Thorpe Biological Procedures Online. 2020; 22(1) [Pubmed] | [DOI] 43 Ex Vivo Fluorescein-Assisted Confocal Laser Endomicroscopy (CONVIVO® System) in Patients With Glioblastoma: Results From a Prospective Study Francesco Acerbi, Bianca Pollo, Camilla De Laurentis, Francesco Restelli, Jacopo Falco, Ignazio G. Vetrano, Morgan Broggi, Marco Schiariti, Irene Tramacere, Paolo Ferroli, Francesco DiMeco Frontiers in Oncology. 2020; 10 [Pubmed] | [DOI] 44 Multiphoton Microscopy of Oral Tissues: Review Rosa M. Martínez-Ojeda, María D. Pérez-Cárceles, Lavinia C. Ardelean, Stefan G. Stanciu, Juan M. Bueno Frontiers in Physics. 2020; 8 [Pubmed] | [DOI] 45 Intensity-based registration of bright-field and second-harmonic generation images of histopathology tissue sections Adib Keikhosravi, Bin Li, Yuming Liu, Kevin W. Eliceiri Biomedical Optics Express. 2020; 11(1): 160 [Pubmed] | [DOI] 46 Multiphoton microscopy of the dermoepidermal junction and automated identification of dysplastic tissues with deep learning Mikko J. Huttunen, Radu Hristu, Adrian Dumitru, Iustin Floroiu, Mariana Costache, Stefan G. Stanciu Biomedical Optics Express. 2020; 11(1): 186 [Pubmed] | [DOI] 47 THE EYE OF CRAB-EATING FOX (CERDOCYON THOUS): ANATOMICAL CHARACTERISTICS AND NORMATIVE VALUES OF SELECTED DIAGNOSTIC TESTS, MORPHOMETRY OF CORNEAL TISSUE, AND ARRANGEMENTS OF CORNEAL STROMAL COLLAGEN FIBERS Roberta Renzo, Marcela Aldrovani, Roberta M. Crivelaro, Roberto Thiesen, Alexandre A. F. de Barros Sobrinho, Camila P. Balthazar da Silveira, Amanda P. Garcia, Gabrielle C. S. Campos, Karin Werther, José L. Laus Journal of Zoo and Wildlife Medicine. 2020; 51(2): 280 [Pubmed] | [DOI] 48 Quantification of Drugs in Distinctly Separated Ocular Substructures of Albino and Pigmented Rats Anna-Kaisa Rimpelä, Michel Garneau, Katja S. Baum-Kroker, Tanja Schönberger, Frank Runge, Achim Sauer Pharmaceutics. 2020; 12(12): 1174 [Pubmed] | [DOI] 49 Challenges of Post-measurement Histology for the Dielectric Characterisation of Heterogeneous Biological Tissues Alessandra La Gioia, Martin O’Halloran, Emily Porter Sensors. 2020; 20(11): 3290 [Pubmed] | [DOI] 50 Keratinocyte Dissociation (Desmolysis/Acantholysis) in Ameloblastoma Sachin C. Sarode, Gargi S. Sarode, Praveen Birur, Yaser A. Alhazmi, Shankargouda Patil Clinics and Practice. 2020; 10(2): 31 [Pubmed] | [DOI] 51 Renal Papillary Rarefaction: An Artifact Mimicking Papillary Necrosis John Curtis Seely, Sabine Francke, Steven R. Mog, Kendall S. Frazier, Gordon C. Hard Toxicologic Pathology. 2019; 47(5): 645 [Pubmed] | [DOI] 52 Nonproliferative and Proliferative Lesions of the Rat and Mouse Hematolymphoid System Cynthia L. Willard-Mack, Susan A. Elmore, William C. Hall, Johannes Harleman, C. Frieke Kuper, Patricia Losco, Jerold E. Rehg, Christine Rühl-Fehlert, Jerrold M. Ward, Daniel Weinstock, Alys Bradley, Satoru Hosokawa, Gail Pearse, Beth W. Mahler, Ronald A. Herbert, Charlotte M. Keenan Toxicologic Pathology. 2019; 47(6): 665 [Pubmed] | [DOI] 53 Cellular Composition in the Aging Cerebral Cortex of Humans V. P. Kalanjati, M. W. Hendrata, F. N. Ardana Neurophysiology. 2019; 51(6): 424 [Pubmed] | [DOI] 54 Clinical and biological characterization of skeletal muscle tissue biopsies of surgical cancer patients Ana Anoveros-Barrera, Amritpal S. Bhullar, Cynthia Stretch, Nina Esfandiari, Abha R. Dunichand-Hoedl, Karen J.B. Martins, David Bigam, Rachel G. Khadaroo, Todd McMullen, Oliver F. Bathe, Sambasivarao Damaraju, Richard J. Skipworth, Charles T. Putman, Vickie E. Baracos, Vera C. Mazurak Journal of Cachexia, Sarcopenia and Muscle. 2019; 10(6): 1356 [Pubmed] | [DOI] 55 Artificial Intelligence and Digital Pathology: Challenges and Opportunities Hamid Reza Tizhoosh, Liron Pantanowitz Journal of Pathology Informatics. 2018; 9(1): 38 [Pubmed] | [DOI] 56 Troubleshooting in Immunohistochemistry with their Remedies Shankargouda B Patil, Vanishri C Haragannavar, Shwetha K Nambiar World Journal of Dentistry. 2018; 9(4): 333 [Pubmed] | [DOI] 57 Degradation of Bioresorbable Mg–4Zn–1Sr Intramedullary Pins and Associated Biological Responses in Vitro and in Vivo Aaron F. Cipriano, Jiajia Lin, Alan Lin, Amy Sallee, Belinda Le, Mayra Celene Cortez Alcaraz, Ren-Guo Guan, Gary Botimer, Serkan Inceoglu, Huinan Liu ACS Applied Materials & Interfaces. 2017; 9(51): 44332 [Pubmed] | [DOI]