scholarly journals Fluorescence Lifetime Imaging and Spectroscopic Co-Validation for Protoporphyrin IX-Guided Tumor Visualization in Neurosurgery

2021 ◽  
Vol 11 ◽  
Author(s):  
David Reichert ◽  
Mikael T. Erkkilae ◽  
Johanna Gesperger ◽  
Lisa I. Wadiura ◽  
Alexandra Lang ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Fluorescence Lifetime ◽  
Protoporphyrin Ix ◽  
Low Grade ◽  
Light Illumination ◽  
Fluorescence Lifetime Imaging ◽  
High Grade ◽  
Low Grade Gliomas ◽  
Lifetime Imaging ◽  
High Grade Gliomas

Maximal safe resection is a key strategy for improving patient prognosis in the management of brain tumors. Intraoperative fluorescence guidance has emerged as a standard in the surgery of high-grade gliomas. The administration of 5-aminolevulinic acid prior to surgery induces tumor-specific accumulation of protoporphyrin IX, which emits red fluorescence under blue-light illumination. The technology, however, is substantially limited for low-grade gliomas and weakly tumor-infiltrated brain, where low protoporphyrin IX concentrations are outweighed by tissue autofluorescence. In this context, fluorescence lifetime imaging has shown promise to distinguish spectrally overlapping fluorophores. We integrated frequency-domain fluorescence lifetime imaging in a surgical microscope and combined it with spatially registered fluorescence spectroscopy, which can be considered a research benchmark for sensitive protoporphyrin IX detection. Fluorescence lifetime maps and spectra were acquired for a representative set of fresh ex-vivo brain tumor specimens (low-grade gliomas n = 15, high-grade gliomas n = 80, meningiomas n = 41, and metastases n = 35). Combining the fluorescence lifetime with fluorescence spectra unveiled how weak protoporphyrin IX accumulations increased the lifetime respective to tissue autofluorescence. Infiltration zones (4.1ns ± 1.8ns, p = 0.017) and core tumor areas (4.8ns ± 1.3ns, p = 0.040) of low-grade gliomas were significantly distinguishable from non-pathologic tissue (1.6ns ± 0.5ns). Similarly, fluorescence lifetimes for infiltrated and reactive tissue as well as necrotic and core tumor areas were increased for high-grade gliomas and metastasis. Meningioma tumor specimens showed strongly increased lifetimes (12.2ns ± 2.5ns, p = 0.005). Our results emphasize the potential of fluorescence lifetime imaging to optimize maximal safe resection in brain tumors in future and highlight its potential toward clinical translation.

scholarly journals Macroscopic fluorescence-lifetime imaging of NADH and protoporphyrin IX improves the detection and grading of 5-aminolevulinic acid-stained brain tumors

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mikael T. Erkkilä ◽  
David Reichert ◽  
Johanna Gesperger ◽  
Barbara Kiesel ◽  
Thomas Roetzer ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Fluorescence Lifetime ◽  
Tumor Tissue ◽  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
Low Grade ◽  
Wide Field ◽  
Fluorescence Lifetime Imaging ◽  
Lifetime Imaging

AbstractMaximal safe tumor resection remains the key prognostic factor for improved prognosis in brain tumor patients. Despite 5-aminolevulinic acid-based fluorescence guidance the neurosurgeon is, however, not able to visualize most low-grade gliomas (LGG) and infiltration zone of high-grade gliomas (HGG). To overcome the need for a more sensitive visualization, we investigated the potential of macroscopic, wide-field fluorescence lifetime imaging of nicotinamide adenine dinucleotide (NADH) and protoporphyrin IX (PPIX) in selected human brain tumors. For future intraoperative use, the imaging system offered a square field of view of 11 mm at 250 mm free working distance. We performed imaging of tumor tissue ex vivo, including LGG and HGG as well as brain metastases obtained from 21 patients undergoing fluorescence-guided surgery. Half of all samples showed visible fluorescence during surgery, which was associated with significant increase in PPIX fluorescence lifetime. While the PPIX lifetime was significantly different between specific tumor tissue types, the NADH lifetimes did not differ significantly among them. However, mainly necrotic areas exhibited significantly lower NADH lifetimes compared to compact tumor in HGG. Our pilot study indicates that combined fluorescence lifetime imaging of NADH/PPIX represents a sensitive tool to visualize brain tumor tissue not detectable with conventional 5-ALA fluorescence.

scholarly journals Comparison of Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging and Arterial Spin Labeling MR Imaging in Gliomas

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yuankai Lin ◽  
Jianrui Li ◽  
Zhiqiang Zhang ◽  
Qiang Xu ◽  
Zhenyu Zhou ◽  
...  
Keyword(s):  
Diffusion Coefficient ◽  
White Matter ◽  
Mr Imaging ◽  
Arterial Spin Labeling ◽  
Spin Labeling ◽  
Intravoxel Incoherent Motion ◽  
Low Grade ◽  
High Grade ◽  
Low Grade Gliomas ◽  
High Grade Gliomas

Gliomas grading is important for treatment plan; we aimed to investigate the application of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in gliomas grading, by comparing with the three-dimensional pseudocontinuous arterial spin labeling (3D pCASL). 24 patients (13 high grade gliomas and 11 low grade gliomas) underwent IVIM DWI and 3D pCASL imaging before operation; maps of fast diffusion coefficient (D∗), slow diffusion coefficient (D), fractional perfusion-related volume (f), and apparent diffusion coefficient (ADC) as well as cerebral blood flow (CBF) were calculated and then coregistered to generate the corresponding parameter values. We found CBF andD∗were higher in the high grade gliomas, whereas ADC,D, andfwere lower (allP<0.05). In differentiating the high from low grade gliomas, the maximum areas under the curves (AUC) ofD∗, CBF, and ADC were 0.857, 0.85, and 0.902, respectively. CBF was negatively correlated withfin tumor (r=-0.619,P=0.001). ADC was positively correlated withDin both tumor and white matter (r=0.887,P=0.000andr=0.824,P=0.000, resp.). There was no correlation between CBF andD∗in both tumor and white matter (P>0.05). IVIM DWI showed more efficiency than 3D pCASL but less validity than conventional DWI in differentiating the high from low grade gliomas.

scholarly journals Antibiotic Allergy and Blood Eosinophils Percent Could Be Prognostic Indicators of Glioma

2021 ◽  
Author(s):  
Liming Cao ◽  
Zhanghua Lv ◽  
Weiliang Wang ◽  
Xue Li ◽  
Jing Shi ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Tumor Grade ◽  
Blood Eosinophil ◽  
Low Grade ◽  
High Grade ◽  
Cox Regression Analysis ◽  
Low Grade Gliomas ◽  
Antibiotic Allergy ◽  
High Grade Gliomas

Abstract Background: Antibiotic allergy and blood eosinophil percentage (EOS%) may play an important role in the prognosis of gliomas, but few studies reported the relationship between antibiotic allergy and glioma as well as EOS% and glioma. The aim of our study was to estimate the relationships between antibiotic allergy, blood eosinophil percentage (EOS%) and glioma prognosis and to conduct a nomogram model for glioma patients. Estimating the effect of antibiotic allergy and EOS% on glioma prognosis may conduce to finding low-cost and safe prognostic indicators of glioma.Methods: We conducted a retrospective cohort study with 656 glioma patients to estimate the associations between antibiotic allergy, EOS% and glioma prognosis by Kaplan-Meier and Cox regression analysis. Stratified analyses were performed according to tumor grade. We constructed a nomogram with age at diagnosis, gender, tumor grade, antibiotic allergy, EOS% to predict the survival probabilities of glioma. Results: During 12 months follow-up, a total of 227 patients were alive and 318 patients died. Antibiotic allergy and EOS% >1.65 conferred a survival advantage on glioma patients. In the stratified analysis by tumor grade, antibiotic allergy was significantly associated with the prognosis of the prognosis of low-grade gliomas (HR = 0.36, 95%CI: 0.13-0.97) and high-grade gliomas (HR = 0.58, 95%CI: 0.36-0.93) in the univariate Cox regression analysis. However, after adjusting for confounding factors in the multivariate Cox regression analysis, antibiotic allergy was only significantly associated with high-grade gliomas (HRadj = 0.50, 95%CI: 0.30-0.82); the relationship between EOS% and glioma prognosis was restricted to low-grade gliomas (HRadj = 0.50, 95%CI: 0.30-0.82). The C-index of nomogram was 0.74.Conclusions: Antibiotic allergy was a protective prognosis factor of high-grade gliomas, EOS% >1.65 was a protective prognosis factor of low-grade gliomas. The nomogram with antibiotic allergy and EOS% could effectively predict the survival probability of glioma.

scholarly journals 5-Aminolevulinic Acid–Protoporphyrin IX Fluorescence-Guided Surgery for CNS Tumors

2018 ◽  
Vol 27 (1) ◽  
pp. 13-19
Author(s):  
Ricardo Ramina ◽  
Erasmo Barros Da Silva Júnior ◽  
Maurício Coelho Neto ◽  
Leonardo Gilmone Ruschel ◽  
Felipe Andrés Constanzo Navarrette
Keyword(s):  
Aminolevulinic Acid ◽  
Protoporphyrin Ix ◽  
High Grade Glioma ◽  
Awake Surgery ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
High Grade ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
High Grade Gliomas

Introduction: In the last two decades the 5-aminolevulinic acid (5-ALA) has been utilized in primary brain lesions and metastases surgery to aid the identification of tumor limits and infiltration. Objectives: In this retrospective study, we demonstrate our experience with the first 41 cases Latin America of surgical resection of central nervous system (CNS) lesions with 5-ALA. Methods: In 41 consecutive patients, we recorded age, sex, histopathological diagnosis, intraoperative 5-ALA fluorescence tumor response, 5-ALA post-resection resection grade through magnetic resonance image (MRI) and other concomitantintra-operative techniques utilized (transoperative imaging, awake surgery, electrophysiological stimulation and monitoring). Results: Twenty seven high-grade gliomas and 4 non-glial lesions were 5-ALA fluorescence positive; 6 low-grade gliomas, 1 high-grade glioma and a hippocampal gliosis were 5-ALA fluorescence negative. In one case of a low-grade glioma, the patient developed a cardiac arrhythmia, probably not related to 5-ALA administration, but the surgery was suspended. Conclusions: 5-ALA fluorescence-guided surgery is a safe and easy technique to be used, increasing tumor total gross resection in glioma cases, proving to be an invaluable neurosurgical tool for intracranial tumor surgery. There was no serious side effect in this series. This dye should be utilized in all cases of high-grade gliomas. 

Influence of dexamethasone on visible 5-ALA fluorescence and quantitative protoporphyrin IX accumulation measured by fluorescence lifetime imaging in glioblastomas: is pretreatment obligatory before fluorescence-guided surgery?

2021 ◽  
pp. 1-9
Author(s):  
Lisa I. Wadiura ◽  
David Reichert ◽  
Veronika Sperl ◽  
Alexandra Lang ◽  
Barbara Kiesel ◽  
...  
Keyword(s):  
Fluorescence Lifetime ◽  
Aminolevulinic Acid ◽  
Ex Vivo ◽  
Protoporphyrin Ix ◽  
Fluorescence Lifetime Imaging ◽  
Lifetime Imaging ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Significant Difference ◽  
The Mean

OBJECTIVE Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is nowadays widely applied for improved resection of glioblastomas (GBMs). Initially, pretreatment with dexamethasone was considered to be essential for optimal fluorescence effect. However, recent studies reported comparably high rates of visible fluorescence in GBMs despite absence of dexamethasone pretreatment. Recently, the authors proposed fluorescence lifetime imaging (FLIM) for the quantitative analysis of 5-ALA–induced protoporphyrin IX (PpIX) accumulation. The aim of this study was thus to investigate the influence of dexamethasone on visible fluorescence and quantitative PpIX accumulation. METHODS The authors prospectively analyzed the presence of visible fluorescence during surgery in a cohort of patients with GBMs. In this study, patients received dexamethasone preoperatively only if clinically indicated. One representative tumor sample was collected from each GBM, and PpIX accumulation was analyzed ex vivo by FLIM. The visible fluorescence status and mean FLIM values were correlated with preoperative intake of dexamethasone. RESULTS In total, two subgroups with (n = 27) and without (n = 20) pretreatment with dexamethasone were analyzed. All patients showed visible fluorescence independent from preoperative dexamethasone intake. Furthermore, the authors did not find a statistically significant difference in the mean FLIM values between patients with and without dexamethasone pretreatment (p = 0.097). CONCLUSIONS In this first study to date, the authors found no significant influence of dexamethasone pretreatment on either visible 5-ALA fluorescence during GBM surgery or PpIX accumulation based on FLIM. According to these preliminary data, the authors recommend administering dexamethasone prior to fluorescence-guided surgery of GBMs only when clinically indicated.

Correlation of dual energy computed tomography electron density measurements with cerebral glioma grade

2021 ◽  
pp. 197140092110474
Author(s):  
Ritwik Chakrabarti ◽  
Vivek Gupta ◽  
Sameer Vyas ◽  
Kirti Gupta ◽  
Vikram Singh
Keyword(s):  
Computed Tomography ◽  
Electron Density ◽  
Dual Energy ◽  
Low Grade ◽  
High Grade ◽  
Cerebral Glioma ◽  
Density Measurements ◽  
Dual Energy Computed Tomography ◽  
Low Grade Gliomas ◽  
High Grade Gliomas

Objective To correlate dual energy computed tomography electron density measurements with histopathological cerebral glioma grading to determine whether it can be used as a non-invasive predictor of cerebral glioma grade. Materials and methods Fifty patients with suspected cerebral gliomas on imaging scheduled to undergo resection were included. We tested our hypothesis that with increasing glioma grade, increased tumor cellularity should translate into increased electron density and if a statistically significant difference between electron density of low-grade gliomas and high-grade gliomas is seen, we may have a clinical use of dual energy computed tomography as a non-invasive tool to predict cerebral glioma grade. A pre-operative dual energy computed tomography scan of the brain was performed, and electron density measurements calculated from the solid part of the tumor. Obtaining a ratio with electron density of contralateral normal brain parenchyma normalized these values. The minimum, maximum and mean electron density and their normalized values recorded between high-grade gliomas and low-grade gliomas were compared for presence of statistical significance. Results A statistically significant difference was found between all six parameters recorded (minimum electron density and normalized values, mean electron density and normalized values, maximum electron density and normalized values) between low-grade gliomas and high-grade gliomas. The predictivity ranged from 75% (for minimum electron density and maximum normalized values) to 81.25% (for mean normalized values). All six parameters were found to have statistically significant positive correlation with Ki-67 index. Conclusion Dual energy computed tomography electron density measurements in cerebral gliomas are predictive of pre-operative differentiation of low-grade gliomas from high-grade gliomas and show a linear, statistically significant positive correlation with Ki-67 index.

scholarly journals Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

2014 ◽  
Vol 36 (2) ◽  
pp. E10 ◽  
Author(s):  
Serge Marbacher ◽  
Elisabeth Klinger ◽  
Lucia Schwyzer ◽  
Ingeborg Fischer ◽  
Edin Nevzati ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Brain Tumors ◽  
Brain Metastases ◽  
Low Grade ◽  
High Grade ◽  
Open Resection ◽  
Who Grade ◽  
Primary Brain Tumors ◽  
High Grade Gliomas ◽  
Surgical Adjunct

Object The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)–induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases. Methods The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA–guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence. Results A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA–positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA–positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA–positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes. Conclusions Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.

scholarly journals Arterial spin labeling in the grading of brain gliomas: could it help?

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Ahmed A. ElBeheiry ◽  
Doaa M. Emara ◽  
Amany Abdel-Bary Abdel-Latif ◽  
Mohamed Abbas ◽  
Amal S. Ismail
Keyword(s):  
Perfusion Imaging ◽  
Arterial Spin Labeling ◽  
Spin Labeling ◽  
High Morbidity ◽  
Low Grade ◽  
Dynamic Susceptibility ◽  
High Grade ◽  
Low Grade Gliomas ◽  
High Grade Gliomas ◽  
Brain Gliomas

Abstract Background Gliomas are characterized by high morbidity and mortality with low cure and high recurrence rates, which depends to a great degree on the angiogenesis of the tumor. Assessment of such angiogenesis by perfusion techniques is of utmost importance for the preoperative grading of gliomas. The purpose of this study was to assess the role of arterial spin labeling (ASL) perfusion as a non-contrast MRI technique in the grading of brain gliomas, in correlation with the dynamic susceptibility contrast perfusion imaging (DSC-PI). The study was carried out on 35 patients admitted to the Neurosurgery Department with MRI features of gliomas and sent for further perfusion imaging. Non-contrast ASL followed by DSC-PI was done for all cases. The final diagnosis of the cases was established by histopathology. Results Fourteen patients (14/35) had low-grade gliomas while twenty-one (21/35) had high-grade gliomas. In low-grade gliomas, four cases out of 14 were falsely graded as high-grade tumors showing hyperperfusion on ASL, three of which showed DSC-PI hypoperfusion. In high-grade gliomas, two cases out of 21 were interpreted as an indeterminate grade by ASL showing isoperfusion, however showed hyperperfusion on DSC-PI. ROC curve analysis showed ASL-derived rCBF > 2.08 to have 80.95% sensitivity, 85.71% specificity, and overall accuracy of 82.86% compared to 100% sensitivity, specificity, and accuracy of DSC-PI-derived rCBV and rCBF of > 1.1 and > 0.9, respectively. A significant positive correlation was noted between ASL and DSC-PI with correlation coefficient reaching r = 0.80 between ASL-rCBF and DSC-rCBF (p < 0.01) and r = 0.68 between ASL and DSC-rCBV (p < 0.01). Conclusions ASL is a relatively recent non-contrast perfusion technique that obtains results which are in fair agreement with the more established DSC perfusion imaging making it an alternative method for preoperative assessment of perfusion of gliomas, especially for patients with contraindications to contrast agents.

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