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Confocal laser endomicroscopy for diagnosis and histomorphologic imaging of brain tumors in vivo.

Foersch S, Heimann A, Ayyad A, Spoden GA, Florin L, Mpoukouvalas K, Kiesslich R, Kempski O, Goetz M, Charalampaki P - PLoS ONE (2012)

Bottom Line: CLE discrimination of neoplastic from healthy brain tissue was easy to perform based on tissue and cellular architecture and resemblance with histopathology was excellent.Confocal laser endomicroscopy allows immediate in vivo imaging of normal and neoplastic brain tissue at high resolution.The technology might be transferred to scientific and clinical application in neurosurgery and neuropathology.

View Article: PubMed Central - PubMed

Affiliation: Medical Clinic I, University Medical Center, Mainz, Germany.

ABSTRACT
Early detection and evaluation of brain tumors during surgery is crucial for accurate resection. Currently cryosections during surgery are regularly performed. Confocal laser endomicroscopy (CLE) is a novel technique permitting in vivo histologic imaging with miniaturized endoscopic probes at excellent resolution. Aim of the current study was to evaluate CLE for in vivo diagnosis in different types and models of intracranial neoplasia. In vivo histomorphology of healthy brains and two different C6 glioma cell line allografts was evaluated in rats. One cell line expressed EYFP, the other cell line was used for staining with fluorescent dyes (fluorescein, acriflavine, FITC-dextran and Indocyanine green). To evaluate future application in patients, fresh surgical resection specimen of human intracranial tumors (n = 15) were examined (glioblastoma multiforme, meningioma, craniopharyngioma, acoustic neurinoma, brain metastasis, medulloblastoma, epidermoid tumor). Healthy brain tissue adjacent to the samples served as control. CLE yielded high-quality histomorphology of normal brain tissue and tumors. Different fluorescent agents revealed distinct aspects of tissue and cell structure (nuclear pattern, axonal pathways, hemorrhages). CLE discrimination of neoplastic from healthy brain tissue was easy to perform based on tissue and cellular architecture and resemblance with histopathology was excellent. Confocal laser endomicroscopy allows immediate in vivo imaging of normal and neoplastic brain tissue at high resolution. The technology might be transferred to scientific and clinical application in neurosurgery and neuropathology. It may become helpful to screen for tumor free margins and to improve the surgical resection of malignant brain tumors, and opens the door to in vivo molecular imaging of tumors and other neurologic disorders.

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Related in: MedlinePlus

Glioblastoma.Schematic (A) and macroscopic (B) image of resection specimen. Attached to the tumorous tissue (pink), a small piece of healthy brain tissue was observed (purple). Panel C-F - Ex vivo CLE of a fresh surgical resection specimen of healthy brain tissue (C, D) in direct proximity of the glioblastoma specimen (E, F) of the same patient. Healthy brain tissue reveals neuron or microglial cells with appendices (arrows). In comparison to healthy brain tissue the tumor reveals rampant excessive growth with atypic nuclei and abnormal nuclear-to-cytoplasm ratio. Atypic mitoses can be observed. Panel G-J - Ex vivo histopathology confirms the findings and diagnosis found in CLE (healthy brain tissue G, H – glioblastoma I, J).
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pone-0041760-g006: Glioblastoma.Schematic (A) and macroscopic (B) image of resection specimen. Attached to the tumorous tissue (pink), a small piece of healthy brain tissue was observed (purple). Panel C-F - Ex vivo CLE of a fresh surgical resection specimen of healthy brain tissue (C, D) in direct proximity of the glioblastoma specimen (E, F) of the same patient. Healthy brain tissue reveals neuron or microglial cells with appendices (arrows). In comparison to healthy brain tissue the tumor reveals rampant excessive growth with atypic nuclei and abnormal nuclear-to-cytoplasm ratio. Atypic mitoses can be observed. Panel G-J - Ex vivo histopathology confirms the findings and diagnosis found in CLE (healthy brain tissue G, H – glioblastoma I, J).

Mentions: A total of n = 15 fresh biopsy specimens of different intracranial neoplasms and normal cerebral tissue were examined ex vivo with CLE. In all cases acriflavine provided satisfactory contrast for endomicroscopic imaging. Healthy brain tissue attached to a tumor specimen, showed typical cells with large nuclei mostly depicting neurons or cells of glial origin. Smaller interstitial cells were also observed, resembling stromal- or immune cells. Images showed typical characteristics of healthy rat brain tissue. (Figure 6). Human glioblastoma showed rampant and invasive cell growth. As in the C6 glioma allografts, common signs of malignancy could be observed such as nuclear polymorphisms, shift of nuclear-cytoplasm-ratio and high proliferation index, shown by atypical mitoses (Fig. 6).


Confocal laser endomicroscopy for diagnosis and histomorphologic imaging of brain tumors in vivo.

Foersch S, Heimann A, Ayyad A, Spoden GA, Florin L, Mpoukouvalas K, Kiesslich R, Kempski O, Goetz M, Charalampaki P - PLoS ONE (2012)

Glioblastoma.Schematic (A) and macroscopic (B) image of resection specimen. Attached to the tumorous tissue (pink), a small piece of healthy brain tissue was observed (purple). Panel C-F - Ex vivo CLE of a fresh surgical resection specimen of healthy brain tissue (C, D) in direct proximity of the glioblastoma specimen (E, F) of the same patient. Healthy brain tissue reveals neuron or microglial cells with appendices (arrows). In comparison to healthy brain tissue the tumor reveals rampant excessive growth with atypic nuclei and abnormal nuclear-to-cytoplasm ratio. Atypic mitoses can be observed. Panel G-J - Ex vivo histopathology confirms the findings and diagnosis found in CLE (healthy brain tissue G, H – glioblastoma I, J).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3404071&req=5

pone-0041760-g006: Glioblastoma.Schematic (A) and macroscopic (B) image of resection specimen. Attached to the tumorous tissue (pink), a small piece of healthy brain tissue was observed (purple). Panel C-F - Ex vivo CLE of a fresh surgical resection specimen of healthy brain tissue (C, D) in direct proximity of the glioblastoma specimen (E, F) of the same patient. Healthy brain tissue reveals neuron or microglial cells with appendices (arrows). In comparison to healthy brain tissue the tumor reveals rampant excessive growth with atypic nuclei and abnormal nuclear-to-cytoplasm ratio. Atypic mitoses can be observed. Panel G-J - Ex vivo histopathology confirms the findings and diagnosis found in CLE (healthy brain tissue G, H – glioblastoma I, J).
Mentions: A total of n = 15 fresh biopsy specimens of different intracranial neoplasms and normal cerebral tissue were examined ex vivo with CLE. In all cases acriflavine provided satisfactory contrast for endomicroscopic imaging. Healthy brain tissue attached to a tumor specimen, showed typical cells with large nuclei mostly depicting neurons or cells of glial origin. Smaller interstitial cells were also observed, resembling stromal- or immune cells. Images showed typical characteristics of healthy rat brain tissue. (Figure 6). Human glioblastoma showed rampant and invasive cell growth. As in the C6 glioma allografts, common signs of malignancy could be observed such as nuclear polymorphisms, shift of nuclear-cytoplasm-ratio and high proliferation index, shown by atypical mitoses (Fig. 6).

Bottom Line: CLE discrimination of neoplastic from healthy brain tissue was easy to perform based on tissue and cellular architecture and resemblance with histopathology was excellent.Confocal laser endomicroscopy allows immediate in vivo imaging of normal and neoplastic brain tissue at high resolution.The technology might be transferred to scientific and clinical application in neurosurgery and neuropathology.

View Article: PubMed Central - PubMed

Affiliation: Medical Clinic I, University Medical Center, Mainz, Germany.

ABSTRACT
Early detection and evaluation of brain tumors during surgery is crucial for accurate resection. Currently cryosections during surgery are regularly performed. Confocal laser endomicroscopy (CLE) is a novel technique permitting in vivo histologic imaging with miniaturized endoscopic probes at excellent resolution. Aim of the current study was to evaluate CLE for in vivo diagnosis in different types and models of intracranial neoplasia. In vivo histomorphology of healthy brains and two different C6 glioma cell line allografts was evaluated in rats. One cell line expressed EYFP, the other cell line was used for staining with fluorescent dyes (fluorescein, acriflavine, FITC-dextran and Indocyanine green). To evaluate future application in patients, fresh surgical resection specimen of human intracranial tumors (n = 15) were examined (glioblastoma multiforme, meningioma, craniopharyngioma, acoustic neurinoma, brain metastasis, medulloblastoma, epidermoid tumor). Healthy brain tissue adjacent to the samples served as control. CLE yielded high-quality histomorphology of normal brain tissue and tumors. Different fluorescent agents revealed distinct aspects of tissue and cell structure (nuclear pattern, axonal pathways, hemorrhages). CLE discrimination of neoplastic from healthy brain tissue was easy to perform based on tissue and cellular architecture and resemblance with histopathology was excellent. Confocal laser endomicroscopy allows immediate in vivo imaging of normal and neoplastic brain tissue at high resolution. The technology might be transferred to scientific and clinical application in neurosurgery and neuropathology. It may become helpful to screen for tumor free margins and to improve the surgical resection of malignant brain tumors, and opens the door to in vivo molecular imaging of tumors and other neurologic disorders.

Show MeSH
Related in: MedlinePlus