Confocal Microscopy: Clinical Impacts and Innovation, 2nd Edition

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Biomedical Optics".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 1796

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Guest Editor
Department of Neurosurgery, Cologne Medical Center, University Witten, Cologne, Germany
Interests: optic; photonic; confocal microscopy; modern operative techniques; deep machine learning; molecular pathology
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Special Issue Information

Dear Colleagues,

Tumor diagnosis and the definition of tumor borders intraoperatively are based on visualization modalities used by surgeons as well as on the histopathologic examination of a limited number of biopsy specimens. Furthermore, optimal surgical therapy is the combination of maximal near-total resection and minimal injury of normal tissues, achieved only if it is possible to identify intraoperative cellular structures and differentiate tumor tissue from normal functional tissue, in order to resect a tumor completely and protect the normal tissue. To achieve this goal, we need new technological equipment combined with new surgical concepts.

The principle of confocal laser endomicroscopy (CLE), based on extreme miniaturization of the microscope imaging head, offers the possibility of in vivo microscopy with subcellular and subnuclear resolution. Clear visualization of the cytoarchitecture can be achieved with a 400-fold to 1000-fold magnification.

In oncological diagnosis and surgery, CLE would allow, on the one hand, intraoperative detection and differentiation of single tumor cells (without the need of fast biopsies) and, on the other hand, the definition of borders between tumors and normal tissue on a cellular level, making surgical resection much more accurate than ever before. The application and implementation of CLE-assisted surgery in surgical oncology increases not only the diagnostic but also the therapeutic options by extending the resection borders of cancer on a cellular level and, more importantly, by protecting the functionality of normal tissues.

For this Special Issue, we welcome studies from authors working on implementing in vivo and ex vivo surgical and clinical concepts and techniques of confocal laser endomicroscopy in their treatments.

Potential topics of interest include but are not limited to the following:

  • Confocal-assisted surgery for oncologic brain and head and neck surgery as well as for other disciplines related to oncological surgery;
  • New frontiers in fluorescence microscopy used for surgical oncology;
  • Advances in intraoperative visualization modalities regarding tumor differentiation;
  • Implementation of cell imaging in different oncologic working disciplines;
  • New concepts of cellular surgical cancer therapies in the operation theatre;
  • Embedded technological systems for tumor margin differentiation and cellular analysis in thoracic, abdominal, and urological diseases;
  • Deep machine learning techniques for confocal microscopy in pathology.

Prof. Dr. Cleopatra Charalampaki
Guest Editor

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Keywords

  • confocal laser endomicroscopy
  • diagnosis
  • biopsy specimens
  • tumor
  • cell imaging
  • deep machine learning techniques

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Published Papers (2 papers)

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13 pages, 9575 KiB  
Article
In Vivo Confocal Microscopy Findings in Corneal Stromal Dystrophies
by Süleyman Okudan, Emine Tınkır Kayıtmazbatır, Ayşe Bozkurt Oflaz and Banu Bozkurt
Diagnostics 2025, 15(2), 182; https://doi.org/10.3390/diagnostics15020182 - 14 Jan 2025
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Abstract
Background/Objectives: In this study, we aim to evaluate in vivo confocal microscopy (IVCM) findings of corneal stromal dystrophies (CSDs) including granular, macular and lattice corneal dystrophy that can be used for differential diagnosis and monitoring recurrences after surgical interventions. Methods: Patients diagnosed [...] Read more.
Background/Objectives: In this study, we aim to evaluate in vivo confocal microscopy (IVCM) findings of corneal stromal dystrophies (CSDs) including granular, macular and lattice corneal dystrophy that can be used for differential diagnosis and monitoring recurrences after surgical interventions. Methods: Patients diagnosed with CSD who were followed-up in the cornea and ocular surface unit were included in this study. IVCM was performed using the Heidelberg Retina Tomograph 3, Rostock Cornea Module (Heidelberg Engineering, Germany) and anterior segment optical coherence tomography (AS-OCT) imaging was performed using the Spectralis OCT (Heidelberg Engineering, Germany). The morphological structure, size and location of deposits, epithelial involvement and presence of inflammatory and dentritic cells were compared among the three stromal dystrophies. Results: A total of 72 eyes from 36 participants were included in this study. Twelve patients (33.33%) had granular corneal dystrophy (GCD), ten (27.77%) had macular corneal dystrophy (MCD) and fourteen (38.88%) had lattice corneal dystrophy (LCD). In GCD, highly reflective deposits varying in size (20 µm–300 µm) were observed. In MCD, diffuse hyperreflective stroma with dark striae, dentritic cells around deposits and abnormal keratocytes were observed. In LCD, there were branching, lattice-like and granular deposits with epithelial cell disruption in some of the eyes. In MCD, the central corneal thickness was thinner (449.44 ± 65.45 µm) compared to GCD and LCD (565.16 ± 49.62 µm and 569.91 ± 39.32 µm p < 0.001). Recurrence was observed in five patients following penetrating keratoplasty. Conclusions: IVCM is a valuable tool for distinguishing CSD subtypes and monitoring recurrence following surgical interventions. Full article
(This article belongs to the Special Issue Confocal Microscopy: Clinical Impacts and Innovation, 2nd Edition)
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20 pages, 2628 KiB  
Review
Confocal Laser Endomicroscopy: Enhancing Intraoperative Decision Making in Neurosurgery
by Francesco Carbone, Nicola Pio Fochi, Giuseppe Di Perna, Arthur Wagner, Jürgen Schlegel, Elena Ranieri, Uwe Spetzger, Daniele Armocida, Fabio Cofano, Diego Garbossa, Augusto Leone and Antonio Colamaria
Diagnostics 2025, 15(4), 499; https://doi.org/10.3390/diagnostics15040499 - 19 Feb 2025
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Abstract
Brain tumors, both primary and metastatic, represent a significant global health burden due to their high incidence, mortality, and the severe neurological deficits they frequently cause. Gliomas, especially high-grade gliomas (HGGs), rank among the most aggressive and lethal neoplasms, with only modest gains [...] Read more.
Brain tumors, both primary and metastatic, represent a significant global health burden due to their high incidence, mortality, and the severe neurological deficits they frequently cause. Gliomas, especially high-grade gliomas (HGGs), rank among the most aggressive and lethal neoplasms, with only modest gains in long-term survival despite extensive molecular research and established standard therapies. In neurosurgical practice, maximizing the extent of safe resection is a principal strategy for improving clinical outcomes. Yet, the infiltrative nature of gliomas often complicates the accurate delineation of tumor margins. Confocal laser endomicroscopy (CLE), originally introduced in gastroenterology, has recently gained prominence in neuro-oncology by enabling real-time, high-resolution cellular imaging during surgery. This technique allows for intraoperative tumor characterization and reduces dependence on time-consuming frozen-section analyses. Recent technological advances, including device miniaturization and second-generation CLE systems, have substantially improved image quality and diagnostic utility. Furthermore, integration with deep learning algorithms and telepathology platforms fosters automated image interpretation and remote expert consultations, thereby accelerating surgical decision making and enhancing diagnostic consistency. Future work should address remaining challenges, such as mitigating motion artifacts, refining training protocols, and broadening the range of applicable fluorescent probes, to solidify CLE’s role as a critical intraoperative adjunct in neurosurgical oncology. Full article
(This article belongs to the Special Issue Confocal Microscopy: Clinical Impacts and Innovation, 2nd Edition)
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