scholarly journals Second window ICG predicts postoperative MRI gadolinium enhancement in high grade gliomas and brain metastases

2022 ◽  
Vol 6 (1) ◽  
pp. V8
Keyword(s):  
Brain Metastases ◽  
Near Infrared ◽  
Prospective Trial ◽  
High Grade ◽  
Gadolinium Enhancement ◽  
Postoperative Mri ◽  
Nir Imaging ◽  
Residual Neoplasm ◽  
High Grade Gliomas ◽  
Higher Sensitivity

A prospective trial evaluating the utility of second window indocyanine green (SWIG) in predicting postoperative MRI gadolinium enhancement was performed on high-grade gliomas (HGGs) and brain metastases. Compared to white light alone, SWIG demonstrated a higher sensitivity, negative predictive value, and accuracy in predicting residual neoplasm on MRI. The specificity of SWIG for predicting MRI enhancement was higher in HGGs than brain metastases. Clinically, near-infrared (NIR) imaging was better able to predict tumor recurrence than postoperative MRI. These results illustrate how SWIG is able to take advantage of gadolinium-like distribution properties to extravasate into the tumor microenvironment, enabling guidance in surgical resection. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21204

scholarly journals Folate Receptor Near-Infrared Optical Imaging Provides Sensitive and Specific Intraoperative Visualization of Nonfunctional Pituitary Adenomas

2018 ◽  
Vol 16 (1) ◽  
pp. 59-70 ◽  
Author(s):  
Steve S Cho ◽  
Ryan Zeh ◽  
John T Pierce ◽  
Jun Jeon ◽  
MacLean Nasrallah ◽  
...  
Keyword(s):  
Predictive Value ◽  
Pituitary Adenomas ◽  
Near Infrared ◽  
Folate Receptor ◽  
P Value ◽  
Fluorescence Signal ◽  
Postoperative Mri ◽  
Nir Fluorescence ◽  
Residual Neoplasm ◽  
Nir Dye

Abstract BACKGROUND Surgical resection is the primary treatment for nonfunctional (NF) pituitary adenomas, but gross-total resection is difficult to achieve in all cases. NF adenomas overexpress folate receptor alpha (FRα). OBJECTIVE To test the hypothesis that we could target FRα for highly sensitive and specific intraoperative detection of NF adenomas using near-infrared (NIR) imaging. METHODS Fourteen patients with NF pituitary adenoma were infused with the folate analog NIR dye OTL38 preoperatively. NIR fluorescence signal-to-background ratio (SBR) was recorded for each tumor during resection of the adenomas. Extent of surgery was not modified based on the presence or absence of fluorescence. Immunohistochemistry was performed to assess FRα expression in all specimens. Magnetic resonance imaging (MRI) was performed postoperatively to assess residual neoplasm. RESULTS Nine adenomas overexpressed FRα and fluoresced with a NIR SBR of 3.2 ± 0.52, whereas the 5 non-FRα-overexpressing adenomas fluoresced with an SBR of 1.5 ± 0.21. Linear regression demonstrated a significant correlation between intraoperative SBR and the FRα expression (P-value < .001). Analysis of 14 margin samples revealed that the surgeon's impression of the tissue had 83% sensitivity, 100% specificity, 100% positive predictive value, and 89% negative predictive value, while NIR fluorescence had 100% for all values. NIR fluorescence accurately predicted postoperative MRI results in 78% of FRα-overexpressing patients. CONCLUSION Preoperative injection of folate-tagged NIR dye provides strong signal and visualization of NF pituitary adenomas. It is 100% sensitive and specific for detecting margin neoplasm and can predict postoperative MRI findings. Our results suggest that NIR fluorescence may be superior to white-light visualization alone and may improve resection rates in NF pituitary adenomas.

scholarly journals Differentiation between high-grade gliomas and solitary brain metastases: a comparison of five diffusion-weighted MRI models

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiaji Mao ◽  
Weike Zeng ◽  
Qinyuan Zhang ◽  
Zehong Yang ◽  
Xu Yan ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Fractional Anisotropy ◽  
Volume Fraction ◽  
Mean Diffusivity ◽  
Diffusion Kurtosis Imaging ◽  
High Grade ◽  
Diffusion Weighted Mri ◽  
Diffusion Weighted ◽  
High Grade Gliomas ◽  
Solitary Brain Metastases

Abstract Background To compare the diagnostic performance of neurite orientation dispersion and density imaging (NODDI), mean apparent propagator magnetic resonance imaging (MAP-MRI), diffusion kurtosis imaging (DKI), diffusion tensor imaging (DTI) and diffusion-weighted imaging (DWI) in distinguishing high-grade gliomas (HGGs) from solitary brain metastases (SBMs). Methods Patients with previously untreated, histopathologically confirmed HGGs (n = 20) or SBMs (n = 21) appearing as a solitary and contrast-enhancing lesion on structural MRI were prospectively recruited to undergo diffusion-weighted MRI. DWI data were obtained using a q-space Cartesian grid sampling procedure and were processed to generate parametric maps by fitting the NODDI, MAP-MRI, DKI, DTI and DWI models. The diffusion metrics of the contrast-enhancing tumor and peritumoral edema were measured. Differences in the diffusion metrics were compared between HGGs and SBMs, followed by receiver operating characteristic (ROC) analysis and the Hanley and McNeill test to determine their diagnostic performances. Results NODDI-based isotropic volume fraction (Viso) and orientation dispersion index (ODI); MAP-MRI-based mean-squared displacement (MSD) and q-space inverse variance (QIV); DKI-generated radial, mean diffusivity and fractional anisotropy (RDk, MDk and FAk); and DTI-generated radial, mean diffusivity and fractional anisotropy (RD, MD and FA) of the contrast-enhancing tumor were significantly different between HGGs and SBMs (p < 0.05). The best single discriminative parameters of each model were Viso, MSD, RDk and RD for NODDI, MAP-MRI, DKI and DTI, respectively. The AUC of Viso (0.871) was significantly higher than that of MSD (0.736), RDk (0.760) and RD (0.733) (p < 0.05). Conclusion NODDI outperforms MAP-MRI, DKI, DTI and DWI in differentiating between HGGs and SBMs. NODDI-based Viso has the highest performance.

scholarly journals Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging

2018 ◽  
Vol 129 (2) ◽  
pp. 390-403 ◽  
Author(s):  
John Y. K. Lee ◽  
Steve S. Cho ◽  
Ryan Zeh ◽  
John T. Pierce ◽  
Maria Martinez-Lage ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Real Time ◽  
Pituitary Adenomas ◽  
Near Infrared ◽  
Folate Receptor ◽  
Mri Findings ◽  
Null Cell ◽  
Postoperative Mri ◽  
Visual Contrast ◽  
Nir Imaging

OBJECTIVEPituitary adenomas account for approximately 10% of intracranial tumors and have an estimated prevalence of 15%–20% in the general US population. Resection is the primary treatment for pituitary adenomas, and the transsphenoidal approach remains the most common. The greatest challenge with pituitary adenomas is that 20% of patients develop tumor recurrence. Current approaches to reduce recurrence, such as intraoperative MRI, are costly, associated with high false-positive rates, and not recommended. Pituitary adenomas are known to overexpress folate receptor alpha (FRα), and it was hypothesized that OTL38, a folate analog conjugated to a near-infrared (NIR) fluorescent dye, could provide real-time intraoperative visual contrast of the tumor versus the surrounding nonneoplastic tissues. The preliminary results of this novel clinical trial are presented.METHODSNineteen adult patients who presented with pituitary adenoma were enrolled. Patients were infused with OTL38 2–4 hours prior to surgery. A 4-mm endoscope with both visible and NIR light capabilities was used to visualize the pituitary adenoma and its margins in real time during surgery. The signal-to-background ratio (SBR) was recorded for each tumor and surrounding tissues at various endoscope-to-sella distances. Immunohistochemical analysis was performed to assess the FRα expression levels in all specimens and classify patients as having either high or low FRα expression.RESULTSData from 15 patients (4 with null cell adenomas, 1 clinically silent gonadotroph, 1 totally silent somatotroph, 5 with a corticotroph, 3 with somatotrophs, and 1 somatocorticotroph) were analyzed in this preliminary analysis. Four patients were excluded for technical considerations. Intraoperative NIR imaging delineated the main tumors in all 15 patients with an average SBR of 1.9 ± 0.70. The FRα expression level of the adenomas and endoscope-to-sella distance had statistically significant impacts on the fluorescent SBRs. Additional considerations included adenoma functional status and time from OTL38 injection. SBRs were 3.0 ± 0.29 for tumors with high FRα expression (n = 3) and 1.6 ± 0.43 for tumors with low FRα expression (n = 12; p < 0.05). In 3 patients with immunohistochemistry-confirmed FRα overexpression (2 patients with null cell adenoma and 1 patient with clinically silent gonadotroph), intraoperative NIR imaging demonstrated perfect classification of the tumor margins with 100% sensitivity and 100% specificity. In addition, for these 3 patients, intraoperative residual fluorescence predicted postoperative MRI results with perfect concordance.CONCLUSIONSPituitary adenomas and their margins can be intraoperatively visualized with the preoperative injection of OTL38, a folate analog conjugated to NIR dye. Tumor-to-background contrast is most pronounced in adenomas that overexpress FRα. Intraoperative SBR at the appropriate endoscope-to-sella distance can predict adenoma FRα expression status in real time. This work suggests that for adenomas with high FRα expression, it may be possible to identify margins and to predict postoperative MRI findings.

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 CTNI-42. FIRST-IN-HUMAN FLUORESCENCE GUIDED SURGERY OF HIGH-GRADE GLIOMAS USING PANITUMUMAB-IRDYE800

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii51-ii52
Author(s):  
Quan Zhou ◽  
Nynke van den Berg ◽  
Naoki Nishio ◽  
Guolan Lu ◽  
Stefania Chirita ◽  
...  
Keyword(s):  
Near Infrared ◽  
Human Study ◽  
Closed Field ◽  
Normal Brain ◽  
High Grade ◽  
Viable Tumor ◽  
Flat Dose ◽  
Tumor Tissues ◽  
High Grade Gliomas ◽  
Brain Tissues

Abstract INTRODUCTION High-grade gliomas (HGGs) are malignant brain tumors with devastating prognosis. Extent of resection predicts survival in patients, but current neuroimaging approaches lack tumor specificity. The epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in HGGs. We assessed the feasibility of imaging HGGs using a near-infrared fluorescent anti-EGFR antibody. METHODS Nine patients with contrast enhancing HGGs on presurgical MRI scan were systemically infused with a flat dose of either 50mg (n = 4) or 100mg (n = 5) panitumumab-IRDye800, 1–5 days before surgery. Near-infrared fluorescence imaging of tumor and histologically normal brain tissues was performed intraoperatively and ex vivo. Fluorescence was measured as mean fluorescence intensity (MFI), and tumor-to-background ratio (TBR) were calculated by comparing MFIs of tumor and histologically uninvolved tissue. Immunohistopathological staining of EGFR was performed on formalin fixed paraffin embedded tissue sections. RESULTS Both MFI and TBR were positively correlated to panitumumab-IRDye800 dose per body weight (R2 = 0.59 and 0.07, P &lt; 0.0001 and P = 0.046 respectively). The TBR was higher at a 100 mg dose than at 50 mg (2.1 vs. 1.5). The smallest detectable tumor volume in a closed-field setting was 21 mg with 50 mg of dye and 12 mg with 100 mg. On sections of paraffin embedded tissues, positive EGFR protein expression was observed in 88.9% ± 12.4% of tumor tissues and positively correlated with fluorescence. Sensitivity and specificity of tumor fluorescence for viable tumor detection was calculated and fluorescence was found to be highly sensitive (93%) and specific (81%) for viable tumor tissues while normal brain tissues showed minimal fluorescence. No adverse events related to the imaging probe was observed. CONCLUSION This first-in-human study demonstrates the feasibility and safety of antibody based imaging for contrast enhancing high-grade gliomas.

Prospective trial of radiotherapy after hyperbaric oxygenation with chemotherapy for high-grade gliomas

2003 ◽  
Vol 67 (1) ◽  
pp. 63-67 ◽  
Author(s):  
Kazuhiko Ogawa ◽  
Yoshihiko Yoshii ◽  
Osamu Inoue ◽  
Takafumi Toita ◽  
Atsushi Saito ◽  
...  
Keyword(s):  
Hyperbaric Oxygenation ◽  
Prospective Trial ◽  
High Grade ◽  
High Grade Gliomas

Diagnostic role of apparent diffusion coefficient combined with intratumoral susceptibility signals in differentiating high-grade gliomas from brain metastases

2020 ◽  
pp. 197140092098016
Author(s):  
Mustafa Bozdağ ◽  
Ali Er ◽  
Akın Çinkooğlu ◽  
Sümeyye Ekmekçi
Keyword(s):  
Diffusion Coefficient ◽  
Brain Metastases ◽  
Apparent Diffusion Coefficient ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Proliferation Index ◽  
High Grade ◽  
Ki 67 ◽  
Apparent Diffusion ◽  
High Grade Gliomas

Objective The aim of this study was to assess whether tumoral and peritumoral apparent diffusion coefficient values and intratumoral susceptibility signals on susceptibility-weighted imaging could distinguish between high-grade gliomas and brain metastases, and to investigate their associations with the Ki-67 proliferation index. Materials and methods Fifty-seven patients with pathologically confirmed diagnoses of either high-grade glioma or brain metastasis were enrolled in this study (23 with high-grade gliomas and 34 with brain metastases). The minimum and mean apparent diffusion coefficients in the enhancing tumoral region (ADCmin and ADCmean) and the minimum apparent diffusion coefficient in the peritumoral region (ADCedema) were measured from apparent diffusion coefficient maps, and intratumoral susceptibility signal grades acquired by susceptibility-weighted imaging were calculated. Ki-67 proliferation index values were obtained from the hospital database. These parameters were evaluated using the Mann-Whitney U test, independent-sample t-test, Spearman correlation analysis, receiver operating characteristic curve, and logistic regression analyses. Results ADCmean, ADCmin values, and intratumoral susceptibility signal grades in brain metastases were significantly lower than those in high-grade gliomas (all p < 0.05). Ki-67 proliferation index values showed significant correlations with ADCmean, ADCmin, and intratumoral susceptibility signal grade in brain metastases (all p < 0.05), but no correlation was found in high-grade gliomas (all p > 0.05). According to receiver operating characteristic curve analysis, ADCmean achieved the highest diagnostic performance for discriminating high-grade gliomas from brain metastases. Furthermore, the combination of tumoral apparent diffusion coefficient parameters with intratumoral susceptibility signal grade provided a higher area under the curve than univariate parameters. Conclusion The combination of tumoral apparent diffusion coefficient with intratumoral susceptibility signal grade can offer better diagnostic performances for differential diagnosis. Apparent diffusion coefficient and intratumoral susceptibility signal may reflect cellular proliferative activity in brain metastases, but not in high-grade gliomas.

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