scholarly journals Dynamic 18F-FDOPA-PET/MRI for the preoperative evaluation of gliomas: correlation with stereotactic histopathology

2020 ◽  
Vol 7 (6) ◽  
pp. 656-667
Author(s):  
Maria R Ponisio ◽  
Jonathan E McConathy ◽  
Sonika M Dahiya ◽  
Michelle M Miller-Thomas ◽  
Keith M Rich ◽  
...  

Abstract Background MRI alone has limited accuracy for delineating tumor margins and poorly predicts the aggressiveness of gliomas, especially when tumors do not enhance. This study evaluated simultaneous 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (FDOPA)-PET/MRI to define tumor volumes compared to MRI alone more accurately, assessed its role in patient management, and correlated PET findings with histopathology. Methods Ten patients with known or suspected gliomas underwent standard of care surgical resection and/or stereotactic biopsy. FDOPA-PET/MRI was performed prior to surgery, allowing for precise co-registration of PET, MR, and biopsies. The biopsy sites were modeled as 5-mm spheres, and the local FDOPA uptake at each site was determined. Correlations were performed between measures of tumor histopathology, and static and dynamic PET values: standardized uptake values (SUVs), tumor to brain ratios, metabolic tumor volumes, and tracer kinetics at volumes of interest (VOIs) and biopsy sites. Results Tumor FDOPA-PET uptake was visualized in 8 patients. In 2 patients, tracer uptake was similar to normal brain reference with no histological findings of malignancy. Eight biopsy sites confirmed for glioma had FDOPA uptake without T1 contrast enhancement. The PET parameters were highly correlated only with the cell proliferation marker, Ki-67 (SUVmax: r = 0.985, P = .002). In this study, no statistically significant difference between high-grade and low-grade tumors was demonstrated. The dynamic PET analysis of VOIs and biopsy sites showed decreasing time-activity curves patterns. FDOPA-PET imaging directly influenced patient management. Conclusions Simultaneous FDOPA-PET/MRI allowed for more accurate visualization and delineation of gliomas, enabling more appropriate patient management and simplified validation of PET findings with histopathology.

Author(s):  
Wenhao Wu ◽  
Yongji Tian ◽  
Hong Wan ◽  
Yongmei Song ◽  
Junhua Li ◽  
...  

Background:The overall prognosis of brainstem gliomas is very poor, and the current treatment cannot significantly prolong the overall survival of these patients; therefore, studying the molecular biological mechanisms of the occurrence and development of brainstem gliomas has important significance for their treatment. The Wnt/β-catenin signaling pathway is closely associated with the occurrence and development of tumors, but its relationship with brainstem gliomas remains unclear.Methods:This study used Western blot and immunohistochemistry methods to detect the expressions of Wnt/β-catenin signaling pathway-related components such as Wnt-1, Wnt-2, β-catenin and C-myc in six cases of normal brain tissues and 24 cases of brainstem gliomas and analyzed the relationship between their expressions and clinicopathological characteristics.Results:Wnt-1 had no obvious expression in normal brain tissues and did not show any significant difference between high- and low-grade brainstem gliomas; the expressions of Wnt-2, β-catenin and C-myc in high-grade brainstem gliomas were significantly higher than that in low-grade brainstem gliomas and normal brain tissues and were positively correlated with the expression of Ki-67. Moreover, the expressions of Wnt-2 and C-myc were significantly associated with the prognosis of brainstem glioma patients; additionally, there was a trend toward increased β-catenin expression with shorter survival, but there was no statistical difference.Conclusions:Wnt/β-catenin signaling pathway might be abnormally activated and plays an important role in the occurrence and development of brainstem gliomas. Wnt-2, β-catenin and C-myc may be potential targets for brainstem glioma treatment.


2011 ◽  
Vol 115 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Pablo A. Valdés ◽  
Frederic Leblond ◽  
Anthony Kim ◽  
Brent T. Harris ◽  
Brian C. Wilson ◽  
...  

Object Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. Methods The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. Results A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. Conclusions These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.


2021 ◽  
Vol 11 ◽  
Author(s):  
Maximilian A. Kirchner ◽  
Adrien Holzgreve ◽  
Matthias Brendel ◽  
Michael Orth ◽  
Viktoria C. Ruf ◽  
...  

BackgroundProstate specific membrane antigen (PSMA) PET imaging has recently gained attention in glioblastoma (GBM) patients as a potential theranostic target for PSMA radioligand therapy. However, PSMA PET has not yet been established in a murine GBM model. Our goal was to investigate the potential of PSMA PET imaging in the syngeneic GL261 GBM model and to give an outlook regarding the potential of PMSA radioligand therapy in this model.MethodsWe performed an 18F-PSMA-1007 PET study in the orthotopic GL261 model (n=14 GBM, n=7 sham-operated mice) with imaging at day 4, 8, 11, 15, 18 and 22 post implantation. Time-activity-curves (TAC) were extracted from dynamic PET scans (0-120 min p. i.) in a subset of mice (n=4 GBM, n=3 sham-operated mice) to identify the optimal time frame for image analysis, and standardized-uptake-values (SUV) as well as tumor-to-background ratios (TBR) using contralateral normal brain as background were calculated in all mice. Additionally, computed tomography (CT), ex vivo and in vitro18F-PSMA-1007 autoradiographies (ARG) were performed.ResultsTAC analysis of GBM mice revealed a plateau of TBR values after 40 min p. i. Therefore, a 30 min time frame between 40-70 min p. i. was chosen for PET quantification. At day 15 and later, GBM mice showed a discernible PSMA PET signal on the inoculation site, with highest TBRmean in GBM mice at day 18 (7.3 ± 1.3 vs. 1.6 ± 0.3 in shams; p=0.024). Ex vivo ARG confirmed high tracer signal in GBM compared to healthy background (TBRmean 26.9 ± 10.5 vs. 1.6 ± 0.7 in shams at day 18/22 post implantation; p=0.002). However, absolute uptake values in the GL261 tumor remained low (e.g., SUVmean 0.21 ± 0.04 g/ml at day 18) resulting in low ratios compared to dose-relevant organs (e.g., mean tumor-to-kidney ratio 1.5E-2 ± 0.5E-2).ConclusionsAlthough 18F-PSMA-1007 PET imaging of GL261 tumor-bearing mice is feasible and resulted in high TBRs, absolute tumoral uptake values remained low and hint to limited applicability of the GL261 model for PSMA-directed therapy studies. Further investigations are warranted to identify suitable models for preclinical evaluation of PSMA-targeted theranostic approaches in GBM.


2021 ◽  
pp. 34-48
Author(s):  
T. Yu. Skvortsova ◽  
Zh. I. Savintceva ◽  
D. V. Zakhs ◽  
A. F. Gurchin ◽  
A. I. Kholyavin ◽  
...  

The purpose of the study was to explore the correlation between 11С-methionine (Met) uptake measured by combined positron emission and computed tomography (PET/CT) in newly diagnosed cerebral gliomas and tumor proliferative activity as measured by Ki-67 labeling index (Ki-67 LI).The results of PET/CT with 11С-methionine (PET-Met) of 236 adult patients with pretreated glial brain tumors were included in retrospective analysis. The final diagnosis of glioma according to WHO classification of CNS tumors (2007) was based on both histology and immunohistochemistry using Ki-67 antibodies. On PET-Met tumor-to normal brain uptake ratio (TBR) was calculated by dividing maximum Met uptake in the tumor (hot spot 10 mm in diameter) to activity concentration in the contralateral cortex. The Spearmen rank correlation test was used to analyze the relationships between TBR and Ki-67 LI.PET-Met analysis showed that TBR increases with an increase in the aggressiveness of the glial tumor. The differences of TBR values between gliomas grade II vs III and grade III vs IV were significant (p < 0,001). Among grades II-III gliomas Met uptake was significantly higher in oligodendroglial and mixed gliomas than in astrocytomas (p < 0,001), but the differences did not depend on Ki-67 LI.Correlation analysis demonstrated significant correlation between Ki-67 LI and TBR values (r = 0,49, p < 0,05, Spearman rank test). With analyzing glioma subgroups TBR values correlated with Ki-67 LI in diffuse astrocytomas (r = 0,52, p < 0,05), oligodendrogliomas (r = 0,40, p < 0,05), oligoastrocytomas (r = 0,47, p < 0,05) and in high-grade gliomas (r = 0,45, p < 0,05) but not in low-grade gliomas. Comparison between TBR value and Ki-67 LI in each glioma showed a lack of coincidence in 22 % of cases (high Met uptake but low Ki-67 LI and vice versa). The main reasons for such discrepancies were tumor molecular biology or incorrect biopsy target.Met uptake in diffuse gliomas correlates with proliferative activity which justifies the use of PET-Met for glioma grading. In case of mismatch between two biomarkers one should rely on the indicator that implies a higher aggressiveness of the glioma.


2019 ◽  
Vol 100 (2) ◽  
pp. 102-110
Author(s):  
V. A. Byvaltsev ◽  
I. A. Stepanov ◽  
A. I. Kichigin

Objective. To compare the values obtained for the measured diffusion coefficient (MDC) of brain gliomas with cell density and Ki-67 proliferative activity index and to study whether diffusion-weighted MRI (DWMRI) can be used in the preoperative evaluation of the grade of glial tumors.Material and methods. Diffusion-weighted images of 39 patients with brain gliomas were studied. MDC, cell density, and Ki-67 proliferative activity index were calculated for each tumor. The correlation between MDC values, cell density, and Ki-67 proliferative activity index was analyzed.Results. Comparison of the mean values for MDC revealed a significant difference between grades I–II and III–IV tumors. There were statistically significant differences in the mean Ki-67 index between different grades of gliomas. Evaluation of the correlation between MCD and Ki-67 proliferative activity index demonstrated moderate and strong inverse correlations for low- and high-grade tumors, respectively.Conclusion. The procedure using DW-MRI along with MDC calculation can be used as an additional noninvasive method for the preoperative estimation of the grade and proliferative potential of brain gliomas.


2021 ◽  
Author(s):  
Cong Li ◽  
Chang Yi ◽  
Yingshen Chen ◽  
Shaoyan Xi ◽  
Chengcheng Guo ◽  
...  

Abstract Purpose: Differential diagnosis of tumour recurrence (TuR) from treatment effects (TrE), mostly induced by radiotherapy and chemotherapy, is still difficult by using conventional computed tomography (CT) or magnetic resonance (MR) imaging. We have investigated the diagnostic performance of PET/CT with 3 tracers, 13N-NH3, 18F-FDOPA, and 18F-FDG, to identify TuR and TrE in glioma patients following treatment. Methods: Forty-three patients with MR-suspected recurrent glioma were included. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the lesion and the lesion-to-normal grey-matter cortex uptake (L/G) ratio were obtained from each tracer PET/CT. TuR or TrE was determined by histopathology or clinical MR follow-up for at least 6 months. Results: In this cohort, 34 patients were confirmed to have TuR, and 9 patients met the diagnostic standard of TrE. The SUVmax and SUVmean of 13N-NH3 and 18F-FDOPA PET/CT at TuR lesions were significantly higher compared with normal brain tissue (13N-NH3 0.696±0.558, 0.625±0.507 vs 0.486±0.413; 18F-FDOPA 0.455±0.518, 0.415±0.477 vs 0.194±0.203; both P<0.01), but there was no significant difference in 18F-FDG (6.918±3.190, 6.016±2.807 vs 6.356±3.104, P=0.290 and 0.493). L/G ratios of 13N-NH3 and 18F-FDOPA were significantly higher in TuR than in TrE group (13N-NH3, 1.573±0.099 vs 1.025±0.128, P=0.008; 18F-FDOPA, 2.729±0.131 vs 1.514±0.141, P<0.001). The sensitivity, specificity and AUC (area under the curve) by ROC (receiver operating characteristic) analysis were 57.7%, 100% and 0.803, for 13N-NH3; 84.6%, 100% and 0.938, for 18F-FDOPA; and 80.8%, 100%, and 0.952, for the combination, respectively.Conclusion: Our results suggest that although multiple tracer PET/CT may improve differential diagnosis efficacy, for glioma TuR from TrE, 18F-FDOPA PET-CT is the most reliable. The combination of 18F-FDOPA and 13N-NH3 does not increase the diagnostic efficiency, while 18F-FDG is not worthy for differential diagnosis of glioma TuR and TrE.


2018 ◽  
Vol 28 (1) ◽  
pp. 26-30
Author(s):  
Siam Wee Sim ◽  
Fay Xiangzhen Li ◽  
Mon Mon Oo ◽  
Kannan Laksmi Narasimhan ◽  
Anette Sundfor Jacobsen ◽  
...  

Objective: Micturating cystourethrogram (MCUG) has traditionally been recommended as part of the preoperative evaluation of all cases of hydronephrosis. Several studies have shown that the majority of cases with pelviureteric junction obstruction (PUJO) and concomitant vesicoureteral reflux (VUR) were of low-grade and generally resolved spontaneously. We therefore retrospectively evaluated the need for routine MCUG in all cases of PUJO. Methods: We conducted a retrospective review of clinical records of all patients who underwent pyeloplasty in our institution between 2003 and 2015. Data collected included patient demographics, clinical presentation, radiological procedures performed, operative details as well as postoperative outcomes. Results: A total of 119 patients underwent pyeloplasty for PUJO during this study period. MCUG was performed in 88 patients (74%), of whom eight patients had VUR. All eight patients had unilateral PUJO and two patients had bilateral VUR. Only two patients had high-grade VUR (grade 4). These two patients also had hydroureter detected on ultrasound scan (US). All patients with VUR had spontaneous resolution of reflux. While comparing outcomes for patients with and without VUR, there was no statistically significant difference in terms of the need for redo surgery and improvement in differential renal function post-pyeloplasty. Conclusion: The outcome of pyeloplasty appears to be independent of the presence of concomitant VUR. Therefore, we conclude that MCUG does not need to be performed routinely for all PUJO patients. However, patients with history of recurrent urinary tract infection or findings of hydroureter on US should still be investigated with MCUG.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16502-e16502
Author(s):  
Yoshio Yoshida ◽  
Hidehiko Okazawa ◽  
Akiko Shinagawa ◽  
Yasushi Kiyono ◽  
Tetsuya Mori ◽  
...  

e16502 Background: Even in responders of fertility-sparing hormone treatment for uterine endometrial carcinoma (EC) and atypical endometrial hyperplasia (AH) in young women, there have been high potential risks of later developed relapse. The aim of this study was whether changes in FDG and fluoroestradiol (FES) PET parameters following hormone treatment have the prognostic factor in prediction of later developed relapse. Methods: Eight young patients with EC and AH were treated by fertility-sparing treatment with a high-dose of medroxyprogesterone acetate (MPA) for 26 weeks. All patients underwent two FDG and FES-PET scans at baseline and 8 weeks after the beginning of MPA treatment, respectively. For each lesion, metabolic indices were calculated by standardized uptake values (SUV). All patients were followed up for 2 years. Values of FDG-SUV, FES-SUV and FES/FDG SUV ratio of tumors were retrospectively reviewed. The correlation between these parameters and clinical outcome of EC and AH for 2 years was evaluated. Results: An initial complete response was achieved in all patients. Two of 5 responders (40%) with AH and one of three (33%) responders with EC later developed (72-88weeks) relapse. One of those three patients underwent hysterectomy due to no response for additional MPA therapy. The tracer uptake of FDG and FES was decrease in all eight patients after 8 weeks. The FES/FDG ratio was increased in all three patients with later developed relapse, but the FES/FDG ratio was decrease in all patients without recurrence for 8 weeks. There was a significant difference of the change in FES/FDG ratio between later developed relapse patients and no relapse patients (0.113 vs -0.392; p = 0.044). Conclusions: This study suggests that an increase in the FES/FDG ratio after 8 weeks fertility-sparing hormone treatment with a high-dose of MPA may be a useful biomarker for predicting later developed relapse in EC and AH in young women.


2001 ◽  
Vol 15 (4) ◽  
pp. 267-270 ◽  
Author(s):  
Rie Yasui ◽  
Toru Minatogawa ◽  
Naoyuki Kanoh ◽  
Yasuo Nakata ◽  
Akira Kubota

Nasal hemangiopericytoma-like (HPCL) tumor is a rare vascular tumor and should be differentiated from typical hemangiopericytomas (HPCs). This study reports the case of an HPCL tumor in a 77-year-old man with histological and immunohistochemical features. After preoperative evaluation of the blood supply, the dark-red right intranasal tumor was resected completely via the right maxillary sinus. The final histopathological diagnosis was HPCL tumor based on several stains: vimentin (+), α-SMA (+), etc. Moreover, there were few p53 (+) cells and the Ki-67 and topoisomerase IIα labeling indices were both under 5%. These findings indicated that this tumor was a low-grade malignancy. The immunohistochemical investigations used are useful for making the diagnosis of HPCL tumor and determining the treatment, malignancy, and prognosis. (American Journal of Rhinology 15 267–270, 2001)


Author(s):  
Vera C. Keil ◽  
Gerrit H. Gielen ◽  
Bogdan Pintea ◽  
Peter Baumgarten ◽  
Angeliki Datsi ◽  
...  

Abstract Purpose To explore the focal predictability of vascular growth factor expression and neovascularization using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in glioma. Methods 120 brain biopsies were taken in vital tumor, infiltration zone and normal brain tissue of 30 glioma patients: 17 IDH(isocitrate dehydrogenase)-wildtype glioblastoma (GBM), 1 IDH-wildtype astrocytoma °III (together prognostic group 1), 3 IDH-mutated GBM (group 2), 3 anaplastic astrocytomas IDH-mutated (group 3), 4 anaplastic oligodendrogliomas and 2 low-grade oligodendrogliomas (together prognostic group 4). A mixed linear model evaluated the predictabilities of microvessel density (MVD), vascular area ratio (VAR), mean vessel size (MVS), vascular endothelial growth factor and receptors (VEGF-A, VEGFR‑2) and vascular endothelial-protein tyrosine phosphatase (VE-PTP) expression from Tofts model kinetic and model-free curve parameters. Results All kinetic parameters were associated with VEGF‑A (all p < 0.001) expression. Ktrans, kep and ve were associated with VAR (p = 0.006, 0.004 and 0.01, respectively) and MVS (p = 0.0001, 0.02 and 0.003, respectively) but not MVD (p = 0.84, 0.74 and 0.73, respectively). Prognostic groups differed in Ktrans (p = 0.007) and ve (p = 0.004) values measured in the infiltration zone. Despite significant differences of VAR, MVS, VEGF‑A, VEGFR‑2, and VE-PTP in vital tumor tissue and the infiltration zone (p = 0.0001 for all), there was no significant difference between kinetic parameters measured in these zones. Conclusion The DCE-MRI kinetic parameters show correlations with microvascular parameters in vital tissue and also reveal blood-brain barrier abnormalities in the infiltration zones adequate to differentiate glioma prognostic groups.


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