Prediction of Glioma Stemlike Cell Infiltration in the Non-Contrast-Enhancing Area by Quantitative Measurement of Lactate on Magnetic Resonance Spectroscopy in Glioblastoma.
Inoue Akihiro,Nishikawa Masahiro,Ohnishi Takanori,Yano Hajime,Kanemura Yonehiro,Ohtsuka Yoshihiro,Ozaki Saya,Nakamura Yawara,Matsumoto Shirabe,Suehiro Satoshi,Yamashita Daisuke,Shigekawa Seiji,Watanabe Hideaki,Kitazawa Riko,Tanaka Junya,Kunieda Takeharu
BACKGROUND:We previously reported that glioma stemlike cells (GSCs) exist in the area of the tumor periphery showing no gadolinium enhancement on magnetic resonance imaging. In the present work, we analyzed glucose metabolism to investigate whether lactate could be predictive of tumor invasiveness and of use in detection of the tumor invasion area in glioblastoma multiforme (GBM). METHODS:The expression of lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase (PDH) was investigated in 20 patients. In GSC lines, LDH-A and PDH expression also was examined in parallel to assessments of mitochondrial respiration. We then investigated the relationship between lactate/creatine ratios in the tumor periphery measured by magnetic resonance spectroscopy, using learning-compression-model algorithms and phenotypes of GBMs. RESULTS:In 20 GBMs, high-invasive GBM expressed LDH-A at significantly higher expression than did low-invasive GBM, whereas low-invasive GBM showed significantly higher expression of PDH than did high-invasive GBM. The highly invasive GSC line showed higher expression of LDH-A and lower expression of PDH compared with low-invasive GSC lines. The highly invasive GSC line also showed the lowest consumption of oxygen and the lowest production of adenosine triphosphate. Lactate levels, as measured by magnetic resonance spectroscopy, showed a significant positive correlation with LDH-A transcript levels, permitting classification of the GBMs into high-invasive and low-invasive phenotypes based on a cutoff value of 0.66 in the lactate/creatine ratio. CONCLUSIONS:In the tumor periphery area of the highly invasive GBM, aerobic glycolysis was the predominant pathway for glucose metabolism, resulting in the accumulation of lactate. The level of lactate may facilitate prediction of the tumor-infiltrating area on GBM.
The influence of maximum safe resection of glioblastoma on survival in 1229 patients: Can we do better than gross-total resection?
Li Yan Michael,Suki Dima,Hess Kenneth,Sawaya Raymond
Journal of neurosurgery
OBJECTIVE:Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor. The value of extent of resection (EOR) in improving survival in patients with GBM has been repeatedly confirmed, with more extensive resections providing added advantages. The authors reviewed the survival of patients with significant EORs and assessed the relative benefit/risk of resecting 100% of the MRI region showing contrast-enhancement with or without additional resection of the surrounding FLAIR abnormality region, and they assessed the relative benefit/risk of performing this additional resection. METHODS:The study cohort included 1229 patients with histologically verified GBM in whom ≥ 78% resection was achieved at The University of Texas MD Anderson Cancer Center between June 1993 and December 2012. Patients with > 1 tumor and those 80 years old or older were excluded. The survival of patients having 100% removal of the contrast-enhancing tumor, with or without additional resection of the surrounding FLAIR abnormality region, was compared with that of patients undergoing 78% to < 100% EOR of the enhancing mass. Within the first subgroup, the survival durations of patients with and without resection of the surrounding FLAIR abnormality were subsequently compared. The data on patients and their tumor characteristics were collected prospectively. The incidence of 30-day postoperative complications (overall and neurological) was noted. RESULTS:Complete resection of the T1 contrast-enhancing tumor volume was achieved in 876 patients (71%). The median survival time for these patients (15.2 months) was significantly longer than that for patients undergoing less than complete resection (9.8 months; p < 0.001). This survival advantage was achieved without an increase in the risk of overall or neurological postoperative deficits and after correcting for established prognostic factors including age, Karnofsky Performance Scale score, preoperative contrast-enhancing tumor volume, presence of cyst, and prior treatment status (HR 1.53, 95% CI 1.33-1.77, p < 0.001). The effect remained essentially unchanged when data from previously treated and previously untreated groups of patients were analyzed separately. Additional analyses showed that the resection of ≥ 53.21% of the surrounding FLAIR abnormality beyond the 100% contrast-enhancing resection was associated with a significant prolongation of survival compared with that following less extensive resections (median survival times 20.7 and 15.5 months, respectively; p < 0.001). In the multivariate analysis, the previously treated group with < 53.21% resection had significantly shorter survival than the 3 other groups (that is, previously treated patients who underwent FLAIR resection ≥ 53.21%, previously untreated patients who underwent FLAIR resection < 53.21%, and previously untreated patients who underwent FLAIR resection ≥ 53.21%); the previously untreated group with ≥ 53.21% resection had the longest survival. CONCLUSIONS:What is believed to be the largest single-center series of GBM patients with extensive tumor resections, this study supports the established association between EOR and survival and presents additional data that pushing the boundary of a conventional 100% resection by the additional removal of a significant portion of the FLAIR abnormality region, when safely feasible, may result in the prolongation of survival without significant increases in overall or neurological postoperative morbidity. Additional supportive evidence is warranted.
Application of multi-wavelength technique for photoacoustic imaging to delineate tumor margins during maximum-safe resection of glioma: A preliminary simulation study.
Najafzadeh Ebrahim,Ghadiri Hossein,Alimohamadi Maysam,Farnia Parastoo,Mehrmohammadi Mohammad,Ahmadian Alireza
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
Accurate margin delineation and safe maximal resection of glioma is one of the most challenging problems of neurosurgery, due to its close resemblance to normal brain parenchyma. However, different intraoperative visualization methods have been used for real-time intraoperative investigation of the borders of the resection cavity, each having advantages and limitations. This preliminary study was designed to simulate multi-wavelength photoacoustic imaging for brain tumor margin delineation for maximum safe resection of glioma. Since the photoacoustic signal is directly related to the amount of optical energy absorption by the endogenous tissue chromophores such as hemoglobin; it may be able to illustrate the critical structures such as tumor vessels during surgery. The simulation of the optical and acoustic part was done by using Monte-Carlo and k-wave toolbox, respectively. As our simulation results proved, at different wavelengths and depths, the amount of optical absorption for the blood layer is significantly different from others such as normal and tumoral tissues. Furthermore, experimental validation of our approach confirms that, by using multi-wavelengths proportional to the depth of the tumor margin during surgery, tumor margin can be differented using photoacoustic imaging at various depths. Photoacoustic imaging may be considered as a promising imaging modality which combines the spectral contrast of optical imaging as well as the spatial resolution of ultrasound imaging, and may be able to delineate the vascular-rich glioma margins at different depths of the resection cavity during surgery.
In vivo characterization of physiological and metabolic changes related to isocitrate dehydrogenase 1 mutation expcression by multiparametric MRI and MRS in a rat model with orthotopically grafted human-derived glioblastoma cell lines.
Clément Alexandra,Doyen Matthieu,Fauvelle Florence,Hossu Gabriela,Chen Bailiang,Barberi-Heyob Muriel,Hirtz Alex,Stupar Vasile,Lamiral Zohra,Pouget Celso,Gauchotte Guillaume,Karcher Gilles,Beaumont Marine,Verger Antoine,Lemasson Benjamin
NMR in biomedicine
The physiological mechanism induced by the isocitrate dehydrogenase 1 (IDH1) mutation, associated with better treatment response in gliomas, remains unknown. The aim of this preclinical study was to characterize the IDH1 mutation through in vivo multiparametric MRI and MRS. Multiparametric MRI, including the measurement of blood flow, vascularity, oxygenation, permeability, and in vivo MRS, was performed on a 4.7 T animal MRI system in rat brains grafted with human-derived glioblastoma U87 cell lines expressing or not the IDH1 mutation by the CRISPR/Cas9 method, and secondarily characterized with additional ex vivo HR-MAS and histological analyses. In univariate analyses, compared with IDH1-, IDH1+ tumors exhibited higher vascular density (p < 0.01) and better perfusion (p = 0.02 for cerebral blood flow), but lower vessel permeability (p < 0.01 for time to peak (TTP), p = 0.04 for contrast enhancement) and decreased T map values (p = 0.02). Using linear discriminant analysis, vascular density and TTP values were found to be independent MRI parameters for characterizing the IDH1 mutation (p < 0.01). In vivo MRS and ex vivo HR-MAS analysis showed lower metabolites of tumor aggressiveness for IDH1+ tumors (p < 0.01). Overall, the IDH1 mutation exhibited a higher vascularity on MRI, a lower permeability, and a less aggressive metabolic profile. These MRI features may prove helpful to better pinpoint the physiological mechanisms induced by this mutation.
Neurosurgical experience of managing optic pathway gliomas.
Hill Ciaran Scott,Khan Mehdi,Phipps Kim,Green Katherine,Hargrave Darren,Aquilina Kristian
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
BACKGROUND:Optic pathway gliomas (OPGs), also known as visual pathway gliomas, are debilitating tumors that account for 3-5% of all pediatric brain tumors. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of these tumors results in visual loss and blindness, endocrine and hypothalamic dysfunction, hydrocephalus, and premature death. Their involvement of the visual pathways and proximity to other eloquent brain structures typically precludes complete resection or optimal radiation dosing without incurring significant neurological injury. There are various surgical interventions that can be performed in relation to these lesions including biopsy, cerebrospinal fluid diversion, and partial or radical resection, but their role is a source of debate. This study catalogues our surgical experience and patient outcomes in order to support decision-making in this challenging pathology. METHODS:A retrospective review of all cases of OPGs treated in a single center from July 1990 to July 2020. Data was collected on patient demographics, radiographic findings, pathology, and management including surgical interventions. Outcome data included survival, visual function, endocrine, and hypothalamic dysfunction. RESULTS:One hundred twenty-one patients with OPG were identified, and 50 of these patients underwent a total of 104 surgical procedures. These included biopsy (31), subtotal or gross total resection (20 operations in 17 patients), cyst drainage (17), Ommaya reservoir insertion (9), or cerebrospinal fluid diversion (27). During the study period, there was 6% overall mortality, 18% hypothalamic dysfunction, 20% endocrine dysfunction, and 42% had some cognitive dysfunction. At diagnosis 75% of patients had good or moderate visual function in at least one eye, and overall, this improved to 83% at the end of the study period. In comparison the worst eye had good or moderate visual function in 56%, and this reduced to 53%. Baseline and final visual function were poorer in patients who had a surgical resection, but improvements in vision were still found-particularly in the best eye. DISCUSSION/CONCLUSION:OPG are debilitating childhood tumor that have lifelong consequences in terms of visual function and endocrinopathies/hypothalamic dysfunction; this can result in substantial patient morbidity. Decisions regarding management and the role of surgery in this condition are challenging and include cerebrospinal fluid diversion, biopsy, and in highly select cases cystic decompression or surgical resection. In this paper, we review our own experience, outcomes, and surgical philosophy.
T2-FLAIR Mismatch Sign and Response to Radiotherapy in Diffuse Intrinsic Pontine Glioma.
Yamasaki Fumiyuki,Nishibuchi Ikuno,Karakawa Shuhei,Kaichi Yoko,Kolakshyapati Manish,Takano Motoki,Yonezawa Ushio,Imano Nobuki,Taguchi Akira,Shimomura Maiko,Taniguchi Maki,Onishi Shumpei,Okada Satoshi,Awai Kazuo,Sugiyama Kazuhiko,Nagata Yasushi
PURPOSE:The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign was previously reported as a diagnostic indicator of diffuse astrocytoma, isocitrate dehydrogenase-mutant, and 1p/19q noncodeletion. Subsequently, it was reported that the same findings were observed in diffuse intrinsic pontine glioma (DIPG). We investigated the clinical significance of T2-FLAIR mismatch sign in DIPG. METHODS:Twenty-one patients with DIPG (Male: Female = 12:9) were treated at our institute between 2004 and 2019. All patients were treated with local radiotherapy of 54 Gy/30 fractions. The positive T2-FLAIR mismatch sign was defined if it fulfilled the following criteria: (1) T2-FLAIR mismatch volume was >50% of T2 high volume at nonenhanced area, (2) the FLAIR low lesion is not associated with gadolinium enhancement (inside of enhancement or just outside of enhancement defined as edema), and (3) signal-intensity of FLAIR lowest lesion at tumor is lower than the normal cerebellar cortex. RESULTS:In our patient series, T2-FLAIR mismatch sign was found in 5 out of 21 patients. Objective response rate of radiotherapy was 100% in patients positive for T2-FLAIR mismatch, while it was 25.0% in patients negative for T2-FLAIR mismatch, and this difference was statistically significant (p < 0.01, Fisher's exact test). In patients under the age of 18-years, T2-FLAIR mismatch positive had a slightly better prognosis (p < 0.05, Wilcoxon test). CONCLUSION:T2-FLAIR mismatch sign in DIPG may be an indicator for better response to radiotherapy and a better prognostic factor.
Postcentral gyrus resection of opercular gliomas is a risk factor for motor deficits caused by damaging the radiologically invisible arteries supplying the descending motor pathway.
Shibahara Ichiyo,Sato Sumito,Hide Takuichiro,Saito Ryuta,Kanamori Masayuki,Sonoda Yukihiko,Tominaga Teiji,Kumabe Toshihiro
BACKGROUND:Postoperative motor deficits are among the worst morbidities of glioma surgery. We aim to investigate factors associated with postoperative motor deficits in patients with frontoparietal opercular gliomas. METHODS:Thirty-four patients with frontoparietal opercular gliomas were retrospectively investigated. We examined the postoperative ischemic changes and locations obtained from MRI. RESULTS:Twenty-one patients (62%) presented postoperative ischemic changes. Postoperative MRI was featured with ischemic changes, all located at the subcortical area of the resection cavity. Six patients had postoperative motor deficits, whereas 28 patients did not. Compared to those without motor deficits, those with motor deficits were associated with old age, pre- and postcentral gyri resection, and postcentral gyrus resection (P = 0.023, 0,024, and 0.0060, respectively). A merged image of the resected cavity and T1-weighted brain atlas of the Montreal Neurological Institute showed that a critical area for postoperative motor deficits is the origin of the long insular arteries (LIAs) and the postcentral gyrus. Detail anatomical architecture created by the Human Connectome Project database and T2-weighted images showed that the subcortical area of the operculum of the postcentral gyrus is where the medullary arteries supply, and the motor pathways originated from the precentral gyrus run. CONCLUSIONS:We verified that the origin of the LIAs could damage the descending motor pathways during the resection of frontoparietal opercular gliomas. Also, we identified that motor pathways run the subcortical area of the operculum of the postcentral gyrus, indicating that the postcentral gyrus is an unrecognized area of damaging the descending motor pathways.
Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients - a report of the PET/RANO group.
Galldiks Norbert,Niyazi Maximilian,Grosu Anca L,Kocher Martin,Langen Karl-Josef,Law Ian,Minniti Giuseppe,Kim Michelle M,Tsien Christina,Dhermain Frederic,Soffietti Riccardo,Mehta Minesh P,Weller Michael,Tonn Jörg-Christian
The management of patients with glioma usually requires multimodality treatment including surgery, radiotherapy, and systemic therapy. Accurate neuroimaging plays a central role for radiotherapy planning and follow-up after radiotherapy completion. In order to maximize the radiation dose to the tumor and to minimize toxic effects on the surrounding brain parenchyma, reliable identification of tumor extent and target volume delineation is crucial. The use of positron emission tomography (PET) for radiotherapy planning and monitoring in gliomas has gained considerable interest over the last several years, but Class I data are not yet available. Furthermore, PET has been used after radiotherapy for response assessment and to distinguish tumor progression from pseudoprogression or radiation necrosis. Here, the Response Assessment in Neuro-Oncology (RANO) working group provides a summary of the literature and recommendations for the use of PET imaging for radiotherapy of patients with glioma based on published studies, constituting levels 1-3 evidence according to the Oxford Centre for Evidence-based Medicine.
Establishment of age group classification for risk stratification in glioma patients.
Lin Zhiying,Yang Runwei,Li Kaishu,Yi Guozhong,Li Zhiyong,Guo Jinglin,Zhang Zhou,Junxiang Peng,Liu Yawei,Qi Songtao,Huang Guanglong
BACKGROUND:Age is associated with the prognosis of glioma patients, but there is no uniform standard of age-group classification to evaluate the prognosis of glioma patients. In this study, we aimed to establish an age group classification for risk stratification in glioma patients. METHODS:1502 patients diagnosed with gliomas at Nanfang Hospital between 2000 and 2018 were enrolled. The WHO grade of glioma was used as a dependent variable to evaluate the effect of age on risk stratification. The evaluation model was established by logistic regression, and the Akaike information criterion (AIC) value of the model was used to determine the optimal cutoff points for age-classification. The differences in gender, WHO grade, pathological subtype, tumor cell differentiation, tumor size, tumor location, and molecular markers between different age groups were analyzed. The molecular markers included GFAP, EMA, MGMT, P53, NeuN, Oligo2, EGFR, VEGF, IDH1, Ki-67, PR, CD3, H3K27M, TS, and 1p/19q status. RESULTS:The proportion of men with glioma was higher than that of women with glioma (58.3% vs 41.7%). Analysis of age showed that appropriate classifications of age group were 0-14 years old (pediatric group), 15-47 years old (youth group), 48-63 years old (middle-aged group), and ≥ 64 years old (elderly group).The proportions of glioblastoma and large tumor size (4-6 cm) increased with age (p = 0.000, p = 0.018, respectively). Analysis of the pathological molecular markers across the four age groups showed that the proportion of patients with larger than 10% area of Ki-67 expression or positive PR expression increased with age (p = 0.000, p = 0.017, respectively). CONCLUSIONS:Appropriate classifications of the age group for risk stratification are 0-14 years old (pediatric group), 15-47 years old (young group), 48-63 years old (middle age group) and ≥ 64 years old (elderly group). This age group classification is effective in evaluating the risk of glioblastoma in glioma patients.
Cellular plasticity confers migratory and invasive advantages to a population of glioblastoma-initiating cells that infiltrate peritumoral tissue.
Ruiz-Ontañon Patricia,Orgaz Jose L,Aldaz Beatriz,Elosegui-Artola Alberto,Martino Juan,Berciano Maria T,Montero Juan A,Grande Lara,Nogueira Lorena,Diaz-Moralli Santiago,Esparís-Ogando Azucena,Vazquez-Barquero Alfonso,Lafarga Miguel,Pandiella Atanasio,Cascante Marta,Segura Victor,Martinez-Climent Jose A,Sanz-Moreno Victoria,Fernandez-Luna Jose L
Stem cells (Dayton, Ohio)
Glioblastoma (GBM) is associated with infiltration of peritumoral (PT) parenchyma by isolated tumor cells that leads to tumor regrowth. Recently, GBM stem-like or initiating cells (GICs) have been identified in the PT area, but whether these GICs have enhanced migratory and invasive capabilities compared with GICs from the tumor mass (TM) is presently unknown. We isolated GICs from the infiltrated PT tissue and the TM of three patients and found that PT cells have an advantage over TM cells in two-dimensional and three-dimensional migration and invasion assays. Interestingly, PT cells display a high plasticity in protrusion formation and cell shape and their migration is insensitive to substrate stiffness, which represent advantages to infiltrate microenvironments of different rigidity. Furthermore, mouse and chicken embryo xenografts revealed that only PT cells showed a dispersed distribution pattern, closely associated to blood vessels. Consistent with cellular plasticity, simultaneous Rac and RhoA activation are required for the enhanced invasive capacity of PT cells. Moreover, Rho GTPase signaling modulators αVβ3 and p27 play key roles in GIC invasiveness. Of note, p27 is upregulated in TM cells and inhibits RhoA activity. Gene silencing of p27 increased the invasive capacity of TM GICs. Additionally, β3 integrin is upregulated in PT cells. Blockade of dimeric integrin αVβ3, a Rac activator, reduced the invasive capacity of PT GICs in vitro and abrogated the spreading of PT cells into chicken embryos. Thus, our results describe the invasive features acquired by a unique subpopulation of GICs that infiltrate neighboring tissue.
Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy.
Chan June L,Lee Susan W,Fraass Benedick A,Normolle Daniel P,Greenberg Harry S,Junck Larry R,Gebarski Stephen S,Sandler Howard M
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE:The goal of three-dimensional (3-D) conformal radiation is to increase the dose delivered to tumor while minimizing dose to surrounding normal brain. Previously it has been shown that even escalated doses of 70 to 80 Gy have failure patterns that are predominantly local. This article describes the failure patterns and survival seen with high-grade gliomas given 90 Gy using a 3-D conformal intensity-modulated radiation technique. PATIENTS AND METHODS:From April 1996 to April 1999, 34 patients with supratentorial high-grade gliomas were treated to 90 Gy. For those that recurred, failure patterns were defined in terms of percentage of recurrent tumor located within the high-dose region. Recurrences with more than 95% of their volume within the high-dose region were considered central; those with 80% to 95%, 20% to 80%, and less than 20% were considered in-field, marginal, and distant, respectively. RESULTS:The median age was 55 years, and median follow-up was 11.7 months. At time of analysis, 23 (67.6%) of 34 patients had developed radiographic evidence of recurrence. The patterns of failure were 18 (78%) of 23 central, three (13%) of 23 in-field, two (9%) of 23 marginal, and zero (0%) of 23 distant. The median survival was 11.7 months, with 1-year survival of 47.1% and 2-year survival of 12.9%. No significant treatment toxicities were observed. CONCLUSION:Despite dose escalation to 90 Gy, the predominant failure pattern in high-grade gliomas remains local. This suggests that close margins used in highly conformal treatments do not increase the risk of marginal or distant recurrences. Our results indicate that intensification of local radiotherapy with dose escalation is feasible and deserves further evaluation for high-grade gliomas.
Peritumoral edema on MRI at initial diagnosis: an independent prognostic factor for glioblastoma?
Schoenegger K,Oberndorfer S,Wuschitz B,Struhal W,Hainfellner J,Prayer D,Heinzl H,Lahrmann H,Marosi C,Grisold W
European journal of neurology
BACKGROUND:Peritumoral brain edema in glioblastoma patients is a frequently encountered phenomenon that strongly contributes to neurological signs and symptoms. The role of peritumoral edema as a prognostic factor is controversial. MATERIALS AND METHODS:This multi-centre clinical retrospective study included 110 patients with histologically proven glioblastoma. The prognostic impact on overall survival of pre-treatment peritumoral edema detected on MRI-scans was evaluated. All patients had preoperative MRI, surgery, histology, and received standard treatment regimens. Edema on MRI-scans was classified as minor (<1 cm), and major (>1 cm). RESULTS:Our results confirm that peritumoral edema on preoperative MRI is an independent prognostic factor in addition to postoperative Karnofsky performance score (KPS), age, and type of tumor resection. Patients with major edema had significant shorter overall survival compared to patients with minor edema. CONCLUSION:This easily applicable early radiological characterization may contribute to a more subgroup oriented treatment in glioblastoma patients for future trials, as well as in clinical routine.
Histopathological findings in the peritumoral edema area of human glioma.
Wang Xingfu,Liu Xueyong,Chen Yupeng,Lin Guoshi,Mei Wenzhong,Chen Jianwu,Liu Ying,Lin Zhixiong,Zhang Sheng
Histology and histopathology
Peritumoral brain edema (PTBE) is considered to be one of the main biological behaviors of brain glioma. However, the histopathological features of PTBE remain imprecisely defined. We analyzed the histopathological characteristics in the PTBE area of 22 cases of glioma. Microscopically, the pre-existing basic structure in the edema area was still preserved but there were varying degrees of loose tissue. The main components of the edema tissue were scattered invasive tumor cells, reactive cells, and various blood vessel patterns. Invasive tumor cell density was significantly higher in high-grade glioma than in low-grade glioma, and the density was significantly higher in the area near compared to the area far from the glioma. The Ki-67 proliferative index of the invasive tumor cells was higher in high-grade glioma than in low-grade glioma, but the index was not different in the area near compared to the area far from the glioma. The microvessel pattern in PTBE was primarily branching capillary. The microvessel densities (MVDs) of CD34⁺ and CD105⁺ were higher in high-grade glioma and the area near the glioma than in low-grade glioma and the area far from the glioma. Compared to CD34⁺, the MVD of CD105⁺ exhibited a more significant downward trend in terms of distance from the glioma. The most obvious types of reactive cells were reactive astrocytes and activated microglia. The reactive astrocytes were positive for nestin. The activated microglia emerged in the area near the glioma in most cases and in the area far from the glioma in more than half of the cases. In addition, several cases displayed focal collections of small lymphocytes around small blood vessels and tumor cells arranged around a neuronal cell, and a limited number of cases displayed giant dysmorphic neurons in an edematous cortex. Our data indicate that PTBE is a consequence of tissue reconstruction resulting from tumor cell invasion and is an appropriate niche for the growth and spread of glioma cells.
Does age matter? - A MRI study on peritumoral edema in newly diagnosed primary glioblastoma.
Seidel Clemens,Dörner Nils,Osswald Matthias,Wick Antje,Platten Michael,Bendszus Martin,Wick Wolfgang
BACKGROUND:Peritumoral edema is a characteristic feature of malignant glioma related to the extent of neovascularisation and to vascular endothelial growth factor (VEGF) expression.The extent of peritumoral edema and VEGF expression may be prognostic for patients with glioblastoma. As older age is a negative prognostic marker and as VEGF expression is reported to be increased in primary glioblastoma of older patients, age-related differences in the extent of peritumoral edema have been assessed. METHODS:In a retrospective, single-center study, preoperative magnetic resonance imaging (MRI) scans of steroid-naïve patients (n = 122) of all age groups were analysed. Patients with clinically suspected, radiologically likely or known evidence of secondary glioblastoma were not included.Extent of brain edema was determined in a metric quantitative fashion and in a categorical fashion in relation to tumor size. Analysis was done group-wise related to age. Additionally, tumor size, degree of necrosis, superficial or deep location of tumor and anatomic localization in the brain were recorded. RESULTS:The extent of peritumoral edema in patients >65 years (ys) was not different from the edema extent in patients ≤ 65 ys (p = 0.261). The same was true if age groups ≤ 55 ys and ≥ 70 ys were compared (p = 0.308). However, extent of necrosis (p = 0.023), deep tumor localization (p = 0.02) and frontal localisation (p = 0.016) of the tumor were associated with the extent of edema. Tumor size was not linearly correlated to edema extent (Pearson F = 0.094, p = 0.303) but correlated to degree of necrosis (F = 0.355, p < 0.001, Spearman-Rho) and depth of tumor (p < 0.001). In a multifactorial analysis of maximum edema with the uncorrelated factors age, regional location of tumor and degree of necrosis, only the extent of necrosis (p = 0.022) had a significant effect. CONCLUSION:Age at diagnosis does not determine degree of peritumoral edema, and tumor localization in the white matter is associated with greater extent of edema. The area of necrosis is reflective of volume of edema. In summary, the radiographic appearance of a glioblastoma at diagnosis does not reflect biology in the elderly patient.
Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms.
Kelly P J,Daumas-Duport C,Kispert D B,Kall B A,Scheithauer B W,Illig J J
Journal of neurosurgery
Forty patients with previously untreated intracranial glial neoplasms underwent stereotaxic serial biopsies assisted by computerized tomography (CT) and magnetic resonance imaging (MRI). Tumor volumes defined by computer reconstruction of contrast enhancement and low-attenuation boundaries on CT and T1 and T2 prolongation on MRI revealed that tumor volumes defined by T2-weighted MRI scans were larger than those defined by low-attenuation or contrast enhancement on CT scans. Histological analysis of 195 biopsy specimens obtained from various locations within the volumes defined by CT and MRI revealed that: contrast enhancement most often corresponded to tumor tissue without intervening parenchyma; hypodensity corresponded to parenchyma infiltrated by isolated tumor cells or in some instances to tumor tissue in low-grade gliomas or to simple edema; and isolated tumor cell infiltration extended at least as far as T2 prolongation on magnetic resonance images. This information may be useful in planning surgical procedures and radiation therapy in patients with intracranial glial neoplasms.
A clinical perspective on the 2016 WHO brain tumor classification and routine molecular diagnostics.
van den Bent Martin J,Weller Michael,Wen Patrick Y,Kros Johan M,Aldape Ken,Chang Susan
The 2007 World Health Organization (WHO) classification of brain tumors did not use molecular abnormalities as diagnostic criteria. Studies have shown that genotyping allows a better prognostic classification of diffuse glioma with improved treatment selection. This has resulted in a major revision of the WHO classification, which is now for adult diffuse glioma centered around isocitrate dehydrogenase (IDH) and 1p/19q diagnostics. This revised classification is reviewed with a focus on adult brain tumors, and includes a recommendation of genes of which routine testing is clinically useful. Apart from assessment of IDH mutational status including sequencing of R132H-immunohistochemistry negative cases and testing for 1p/19q, several other markers can be considered for routine testing, including assessment of copy number alterations of chromosome 7 and 10 and of TERT promoter, BRAF, and H3F3A mutations. For "glioblastoma, IDH mutated" the term "astrocytoma grade IV" could be considered. It should be considered to treat IDH wild-type grades II and III diffuse glioma with polysomy of chromosome 7 and loss of 10q as glioblastoma. New developments must be more quickly translated into further revised diagnostic categories. Quality control and rapid integration of molecular findings into the final diagnosis and the communication of the final diagnosis to clinicians require systematic attention.
Advanced multimodal imaging in differentiating glioma recurrence from post-radiotherapy changes.
Li Cong,Gan Yanling,Chen Huijing,Chen Yun,Deng Yuer,Zhan Wengang,Tan Qijia,Xie Caijun,Sharma Hari Shanker,Zhang Zhiqiang
International review of neurobiology
Gliomas are the most common malignant primary brain tumor, and their prognosis is extremely poor. Radiotherapy is an important treatment for glioma patients, but the changes caused by radiotherapy have brought difficulties in clinical image evaluation because differentiating glioma recurrence from post-radiotherapy changes including pseudo-progression (PD) and radiation necrosis (RN) remains a challenge. Therefore, accurate and reliable imaging evaluation is very important for making clinical decisions. In recent years, advanced multimodal imaging techniques have been applied to achieve the goal of better differentiating glioma recurrence from post-radiotherapy changes for minimizing errors associated with interpretation of treatment effects. In this review, we discuss the recent applications of advanced multimodal imaging such as diffusion MRI sequences, amide proton transfer MRI sequences, perfusion MRI sequences, MR spectroscopy and multinuclides PET/CT in the evaluation of post-radiotherapy treatment response in glioma patients and highlight their potential role in differentiating post-radiotherapy changes from glioma recurrence.
Accelerated radial diffusion spectrum imaging using a multi-echo stimulated echo diffusion sequence.
Baete Steven H,Boada Fernando E
Magnetic resonance in medicine
PURPOSE:Diffusion spectrum imaging (DSI) provides us non-invasively and robustly with anatomical details of brain microstructure. To achieve sufficient angular resolution, DSI requires a large number of q-space samples, leading to long acquisition times. This need is mitigated here by combining the beneficial properties of Radial q-space sampling for DSI with a Multi-Echo Stimulated Echo Sequence (MESTIM). METHODS:Full 2D k-spaces for each of several q-space samples, along the same radially outward line in q-space, are acquired in one readout train with one spin and three stimulated echoes. RF flip angles are carefully chosen to distribute spin magnetization over the echoes and the DSI reconstruction is adapted to account for differences in diffusion time among echoes. RESULTS:Individual datasets and bootstrapped reproducibility analysis demonstrate image quality and SNR of the more-than-twofold-accelerated RDSI MESTIM sequence. Orientation distribution functions (ODF) and tractography results benefit from the longer diffusion times of the latter echoes in the echo train. CONCLUSION:A MESTIM sequence can be used to shorten RDSI acquisition times significantly without loss of image or ODF quality. Further acceleration is possible by combination with simultaneous multi-slice techniques. Magn Reson Med 79:306-316, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Comparison of compressed sensing diffusion spectrum imaging and diffusion tensor imaging in patients with intracranial masses.
Young Robert J,Tan Ek T,Peck Kyung K,Jenabi Mehrnaz,Karimi Sasan,Brennan Nicole,Rubel Jennifer,Lyo John,Shi Weiji,Zhang Zhigang,Prastawa Marcel,Liu Xiaofeng,Sperl Jonathan I,Fatovic Robin,Marinelli Luca,Holodny Andrei I
Magnetic resonance imaging
PURPOSE:To compare compressed diffusion spectrum imaging (CS-DSI) with diffusion tensor imaging (DTI) in patients with intracranial masses. We hypothesized that CS-DSI would provide superior visualization of the motor and language tracts. MATERIALS AND METHODS:We retrospectively analyzed 25 consecutive patients with intracranial masses who underwent DTI and CS-DSI for preoperative planning. Directionally-encoded anisotropy maps, and streamline hand corticospinal motor tracts and arcuate fasciculus language tracts were graded according to a 3-point scale. Tract counts, anisotropy, and lengths were also calculated. Comparisons were made using exact marginal homogeneity, McNemar's and Wilcoxon signed-rank tests. RESULTS:Readers preferred the CS-DSI over DTI anisotropy maps in 92% of the cases, and the CS-DSI over DTI tracts in 84%. The motor tracts were graded as excellent in 80% of cases for CS-DSI versus 52% for DTI; 58% of the motor tracts graded as acceptable in DTI were graded as excellent in CS-DSI (p=0.02). The language tracts were graded as excellent in 68% for CS-DSI versus none for DTI; 78% of the language tracts graded as acceptable by DTI were graded as excellent by CS-DSI (p<0.001). CS-DSI demonstrated smaller normalized mean differences than DTI for motor tract counts, anisotropy and language tract counts (p≤0.01). CONCLUSION:CS-DSI was preferred over DTI for the evaluation of motor and language white matter tracts in patients with intracranial masses. Results suggest that CS-DSI may be more useful than DTI for preoperative planning purposes.
Generalized diffusion spectrum magnetic resonance imaging (GDSI) for model-free reconstruction of the ensemble average propagator.
Tian Qiyuan,Yang Grant,Leuze Christoph,Rokem Ariel,Edlow Brian L,McNab Jennifer A
Diffusion spectrum MRI (DSI) provides model-free estimation of the diffusion ensemble average propagator (EAP) and orientation distribution function (ODF) but requires the diffusion data to be acquired on a Cartesian q-space grid. Multi-shell diffusion acquisitions are more flexible and more commonly acquired but have, thus far, only been compatible with model-based analysis methods. Here, we propose a generalized DSI (GDSI) framework to recover the EAP from multi-shell diffusion MRI data. The proposed GDSI approach corrects for q-space sampling density non-uniformity using a fast geometrical approach. The EAP is directly calculated in a preferable coordinate system by multiplying the sampling density corrected q-space signals by a discrete Fourier transform matrix, without any need for gridding. The EAP is demonstrated as a way to map diffusion patterns in brain regions such as the thalamus, cortex and brainstem where the tissue microstructure is not as well characterized as in white matter. Scalar metrics such as the zero displacement probability and displacement distances at different fractions of the zero displacement probability were computed from the recovered EAP to characterize the diffusion pattern within each voxel. The probability averaged across directions at a specific displacement distance provides a diffusion property based image contrast that clearly differentiates tissue types. The displacement distance at the first zero crossing of the EAP averaged across directions orthogonal to the primary fiber orientation in the corpus callosum is found to be larger in the body (5.65 ± 0.09 μm) than in the genu (5.55 ± 0.15 μm) and splenium (5.4 ± 0.15 μm) of the corpus callosum, which corresponds well to prior histological studies. The EAP also provides model-free representations of angular structure such as the diffusion ODF, which allows estimation and comparison of fiber orientations from both the model-free and model-based methods on the same multi-shell data. For the model-free methods, detection of crossing fibers is found to be strongly dependent on the maximum b-value and less sensitive compared to the model-based methods. In conclusion, our study provides a generalized DSI approach that allows flexible reconstruction of the diffusion EAP and ODF from multi-shell diffusion data and data acquired with other sampling patterns.
Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers.
Wedeen V J,Wang R P,Schmahmann J D,Benner T,Tseng W Y I,Dai G,Pandya D N,Hagmann P,D'Arceuil H,de Crespigny A J
MRI tractography is the mapping of neural fiber pathways based on diffusion MRI of tissue diffusion anisotropy. Tractography based on diffusion tensor imaging (DTI) cannot directly image multiple fiber orientations within a single voxel. To address this limitation, diffusion spectrum MRI (DSI) and related methods were developed to image complex distributions of intravoxel fiber orientation. Here we demonstrate that tractography based on DSI has the capacity to image crossing fibers in neural tissue. DSI was performed in formalin-fixed brains of adult macaque and in the brains of healthy human subjects. Fiber tract solutions were constructed by a streamline procedure, following directions of maximum diffusion at every point, and analyzed in an interactive visualization environment (TrackVis). We report that DSI tractography accurately shows the known anatomic fiber crossings in optic chiasm, centrum semiovale, and brainstem; fiber intersections in gray matter, including cerebellar folia and the caudate nucleus; and radial fiber architecture in cerebral cortex. In contrast, none of these examples of fiber crossing and complex structure was identified by DTI analysis of the same data sets. These findings indicate that DSI tractography is able to image crossing fibers in neural tissue, an essential step toward non-invasive imaging of connectional neuroanatomy.
Imaging of Primary Brain Tumors and Metastases with Fast Quantitative 3-Dimensional Magnetization Transfer.
Garcia Meritxell,Gloor Monika,Bieri Oliver,Radue Ernst-Wilhelm,Lieb Johanna M,Cordier Dominik,Stippich Christoph
Journal of neuroimaging : official journal of the American Society of Neuroimaging
BACKGROUND AND PURPOSE:This study assesses whether magnetization transfer (MT) imaging provides additive information to conventional MRI in brain tumors. METHODS:MT data of 26 patients with neoplastic and metastatic brain tumors were analyzed at 1.5 T. For the 3 largest tumor groups investigated in this study--glioblastoma multiforme (GBM), meningiomas, and metastases-statistical comparisons were performed. Analyzed MT parameters included the magnetization transfer ratio (MTR) and 4 quantitative MT parameters (qMT): Relaxation times (T1, T2), exchange rate (kf), and macromolecular content (F). Total imaging time of high-resolution whole brain MTR and qMT imaging with balanced steady-state free precession required 9 minutes. Five ROIs were chosen: Contrast-enhancing (T1W-CE), noncontrast-enhancing (T1W-non-CE), proximal hyperintensity (T2W-pSI), distal hyperintensity (T2W-dSI), and a reference (ref). RESULTS:Pathologies showed significant (P < .05) MT changes (MTR and qMT) compared to the reference. The T1W-CE, T1W-non-CE, and T2W-pSI ROIs of GBMs, meningiomas, and metastases showed significant differences in MTR and qMT estimates. Similar MTR with significant different qMT values were observed in several ROIs among different lesions. MT maps (MTR and qMT) indicated changes in tissue appearing unaffected on MRI in most glial tumors. CONCLUSIONS:MTR and qMT imaging enables a better differentiation between brain tumors and provides additive information to MRI.
Tractography-guided surgery of brain tumours: what is the best method to outline the corticospinal tract?
Szmuda T,Kierońska S,Ali S,Słoniewski P,Pacholski M,Dzierżanowski J,Sabisz A,Szurowska E
BACKGROUND:Diffusion tensor imaging (DTI) is the imaging technique used in vivo to visualise white matter pathways. The cortico-spinal tract (CST) belongs to one of the most often delineated tracts preoperatively, although the optimal DTI method has not been established yet. Considering that various regions of interests (ROIs) could be selected, the reproducibility of CST tracking among different centres is low. We aimed to select the most reliable tractography method for outlining the CST for neurosurgeons. MATERIALS AND METHODS:Our prospective study consisted of 32 patients (11 males, 21 females) with a brain tumour of various locations. DTI and T1-weighed image series were acquired prior to the surgery. To draw the CST, the posterior limb of the internal capsule (PLIC) and the cerebral peduncle (CP) were defined as two main ROIs. Together with these main ROIs, another four cortical endpoints were selected: the frontal lobe (FL), the supplementary motor area (SMA), the precentral gyrus (PCG) and the postcentral gyrus (POCG). Based on these ROIs, we composed ten virtual CSTs in DSI Studio. The fractional anisotropy, the mean diffusivity, the tracts' volume, the length and the number were compared between all the CSTs. The degree of the CST infiltration, tumour size, the patients' sex and age were examined. RESULTS:Significant differences in the number of tracts and their volume were observed when the PLIC or the CP stood as a single ROI comparing with the two- ROI method (all p < 0.05). The mean CST volume was 40054U (SD ± 12874) and the number of fibres was 259.3 (SD ± 87.3) when the PLIC was a single ROI. When the CP was a single ROI, almost a half of fibres (147.6; SD ± 64.0) and half of the CST volume (26664U; SD ± 10059U) was obtained (all p < 0.05). There were no differences between the various CSTs in terms of fractional anisotropy, mean diffusivity, the apparent diffusion coefficient, radial diffusivity and the tract length (p > 0.05). The CST was infiltrated by a growing tumour or oedema in 17 of 32 patients; in these cases, the mean and apparent diffusion of the infiltrated CST was significantly higher than in uncompromised CSTs (p = 0.04). CST infiltration did not alter the other analysed parameters (all p > 0.05). CONCLUSIONS:A universal method of DTI of the CST was not developed. However, we found that the CP or the PLIC (with or without FL as the second ROI) should be used to outline the CST.
Pharmacodynamics of mutant-IDH1 inhibitors in glioma patients probed by in vivo 3D MRS imaging of 2-hydroxyglutarate.
Andronesi Ovidiu C,Arrillaga-Romany Isabel C,Ly K Ina,Bogner Wolfgang,Ratai Eva M,Reitz Kara,Iafrate A John,Dietrich Jorg,Gerstner Elizabeth R,Chi Andrew S,Rosen Bruce R,Wen Patrick Y,Cahill Daniel P,Batchelor Tracy T
Inhibitors of the mutant isocitrate dehydrogenase 1 (IDH1) entered recently in clinical trials for glioma treatment. Mutant IDH1 produces high levels of 2-hydroxyglurate (2HG), thought to initiate oncogenesis through epigenetic modifications of gene expression. In this study, we show the initial evidence of the pharmacodynamics of a new mutant IDH1 inhibitor in glioma patients, using non-invasive 3D MR spectroscopic imaging of 2HG. Our results from a Phase 1 clinical trial indicate a rapid decrease of 2HG levels by 70% (CI 13%, P = 0.019) after 1 week of treatment. Importantly, inhibition of mutant IDH1 may lead to the reprogramming of tumor metabolism, suggested by simultaneous changes in glutathione, glutamine, glutamate, and lactate. An inverse correlation between metabolic changes and diffusion MRI indicates an effect on the tumor-cell density. We demonstrate a feasible radiopharmacodynamics approach to support the rapid clinical translation of rationally designed drugs targeting IDH1/2 mutations for personalized and precision medicine of glioma patients.
Combining Diffusion Tensor Metrics and DSC Perfusion Imaging: Can It Improve the Diagnostic Accuracy in Differentiating Tumefactive Demyelination from High-Grade Glioma?
Hiremath S B,Muraleedharan A,Kumar S,Nagesh C,Kesavadas C,Abraham M,Kapilamoorthy T R,Thomas B
AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE:Tumefactive demyelinating lesions with atypical features can mimic high-grade gliomas on conventional imaging sequences. The aim of this study was to assess the role of conventional imaging, DTI metrics ( tensor decomposition), and DSC perfusion in differentiating tumefactive demyelinating lesions and high-grade gliomas. MATERIALS AND METHODS:Fourteen patients with tumefactive demyelinating lesions and 21 patients with high-grade gliomas underwent brain MR imaging with conventional, DTI, and DSC perfusion imaging. Imaging sequences were assessed for differentiation of the lesions. DTI metrics in the enhancing areas and perilesional hyperintensity were obtained by ROI analysis, and the relative CBV values in enhancing areas were calculated on DSC perfusion imaging. RESULTS:Conventional imaging sequences had a sensitivity of 80.9% and specificity of 57.1% in differentiating high-grade gliomas ( = .049) from tumefactive demyelinating lesions. DTI metrics (: tensor decomposition) and DSC perfusion demonstrated a statistically significant difference in the mean values of ADC, the isotropic component of the diffusion tensor, the anisotropic component of the diffusion tensor, the total magnitude of the diffusion tensor, and rCBV among enhancing portions in tumefactive demyelinating lesions and high-grade gliomas ( ≤ .02), with the highest specificity for ADC, the anisotropic component of the diffusion tensor, and relative CBV (92.9%). Mean fractional anisotropy values showed no significant statistical difference between tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI and DSC parameters improved the diagnostic accuracy (area under the curve = 0.901). Addition of a heterogeneous enhancement pattern to DTI and DSC parameters improved it further (area under the curve = 0.966). The sensitivity increased from 71.4% to 85.7% after the addition of the enhancement pattern. CONCLUSIONS:DTI and DSC perfusion add profoundly to conventional imaging in differentiating tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI metrics and DSC perfusion markedly improved diagnostic accuracy.
Differentiation of glioma malignancy grade using diffusion MRI.
Maximov Ivan I,Tonoyan Aram S,Pronin Igor N
Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)
Modern diffusion MR protocols allow one to acquire the multi-shell diffusion data with high diffusion weightings in a clinically feasible time. In the present work we assessed three diffusion approaches based on diffusion and kurtosis tensor imaging (DTI, DKI), and neurite orientation dispersion and density imaging (NODDI) as possible biomarkers for human brain glioma grade differentiation based on the one diffusion protocol. We used three diffusion weightings (so called b-values) equal to 0, 1000, and 2500s/mm with 60 non-coplanar diffusion directions in the case of non-zero b-values. The patient groups of the glioma grades II, III, and IV consist of 8 subjects per group. We found that DKI, and NODDI scalar metrics can be effectively used as glioma grade biomarkers with a significant difference (p<0.05) for grading between low- and high-grade gliomas, in particular, for glioma II versus glioma III grades, and glioma III versus glioma IV grades. The use of mean/axial kurtosis and intra-axonal fraction/orientation dispersion index metrics allowed us to obtain the most feasible and reliable differentiation criteria. For example, in the case of glioma grades II, III, and IV the mean kurtosis is equal to 0.31, 0.51, and 0.90, and the orientation dispersion index is equal to 0.14, 0.30, and 0.59, respectively. The limitations and perspectives of the biophysical diffusion models based on intra-/extra-axonal compartmentalisation for glioma differentiation are discussed.
Metabolic approach for tumor delineation in glioma surgery: 3D MR spectroscopy image-guided resection.
Zhang Jie,Zhuang Dong-Xiao,Yao Cheng-Jun,Lin Ching-Po,Wang Tian-Liang,Qin Zhi-Yong,Wu Jin-Song
Journal of neurosurgery
OBJECT The extent of resection is one of the most essential factors that influence the outcomes of glioma resection. However, conventional structural imaging has failed to accurately delineate glioma margins because of tumor cell infiltration. Three-dimensional proton MR spectroscopy ((1)H-MRS) can provide metabolic information and has been used in preoperative tumor differentiation, grading, and radiotherapy planning. Resection based on glioma metabolism information may provide for a more extensive resection and yield better outcomes for glioma patients. In this study, the authors attempt to integrate 3D (1)H-MRS into neuronavigation and assess the feasibility and validity of metabolically based glioma resection. METHODS Choline (Cho)-N-acetylaspartate (NAA) index (CNI) maps were calculated and integrated into neuronavigation. The CNI thresholds were quantitatively analyzed and compared with structural MRI studies. Glioma resections were performed under 3D (1)H-MRS guidance. Volumetric analyses were performed for metabolic and structural images from a low-grade glioma (LGG) group and high-grade glioma (HGG) group. Magnetic resonance imaging and neurological assessments were performed immediately after surgery and 1 year after tumor resection. RESULTS Fifteen eligible patients with primary cerebral gliomas were included in this study. Three-dimensional (1)H-MRS maps were successfully coregistered with structural images and integrated into navigational system. Volumetric analyses showed that the differences between the metabolic volumes with different CNI thresholds were statistically significant (p < 0.05). For the LGG group, the differences between the structural and the metabolic volumes with CNI thresholds of 0.5 and 1.5 were statistically significant (p = 0.0005 and 0.0129, respectively). For the HGG group, the differences between the structural and metabolic volumes with CNI thresholds of 0.5 and 1.0 were statistically significant (p = 0.0027 and 0.0497, respectively). All patients showed no tumor progression at the 1-year follow-up. CONCLUSIONS This study integrated 3D MRS maps and intraoperative navigation for glioma margin delineation. Optimum CNI thresholds were applied for both LGGs and HGGs to achieve resection. The results indicated that 3D (1)H-MRS can be integrated with structural imaging to provide better outcomes for glioma resection.
Specific DTI seeding and diffusivity-analysis improve the quality and prognostic value of TMS-based deterministic DTI of the pyramidal tract.
Rosenstock Tizian,Giampiccolo Davide,Schneider Heike,Runge Sophia Jutta,Bährend Ina,Vajkoczy Peter,Picht Thomas
OBJECT:Navigated transcranial magnetic stimulation (nTMS) combined with diffusion tensor imaging (DTI) is used preoperatively in patients with eloquent-located brain lesions and allows analyzing non-invasively the spatial relationship between the tumor and functional areas (e.g. the motor cortex and the corticospinal tract [CST]). In this study, we examined the diffusion parameters FA (fractional anisotropy) and ADC (apparent diffusion coefficient) within the CST in different locations and analyzed their interrater reliability and usefulness for predicting the patients' motor outcome with a precise approach of specific region of interest (ROI) seeding based on the color-coded FA-map. METHODS:Prospectively collected data of 30 patients undergoing bihemispheric nTMS mapping followed by nTMS-based DTI fiber tracking prior to surgery of motor eloquent high-grade gliomas were analyzed by 2 experienced and 1 unexperienced examiner. The following data were scrutinized for both hemispheres after tractography based on nTMS-motor positive cortical seeds and a 2nd region of interest in one layer of the caudal pons defined by the color-coded FA-map: the pre- and postoperative motor status (day of discharge und 3 months), the closest distance between the tracts and the tumor (TTD), the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC). The latter as an average within the CST as well as specific values in different locations (peritumoral, mesencephal, pontine). RESULTS:Lower average FA-values within the affected CST as well as higher average ADC-values are significantly associated with deteriorated postoperative motor function (p = 0.006 and p = 0.026 respectively). Segmental analysis within the CST revealed that the diffusion parameters are especially disturbed on a peritumoral level and that the degree of their impairment correlates with motor deficits (FA p = 0.065, ADC p = 0.007). No significant segmental variation was seen in the healthy hemisphere. The interrater reliability showed perfect agreement for almost all analyzed parameters. CONCLUSIONS:Adding diffusion weighted imaging derived information on the structural integrity of the nTMS-based tractography results improves the predictive power for postoperative motor outcome. Utilizing a second subcortical ROI which is specifically seeded based on the color-coded FA map increases the tracking quality of the CST independently of the examiner's experience. Further prospective studies are needed to validate the nTMS-based prediction of the patient's outcome.
A combined diffusion tensor imaging and Ki-67 labeling index study for evaluating the extent of tumor infiltration using the F98 rat glioma model.
Wang Kai,Ha Tingting,Chen Xuzhu,Li Shaowu,Ai Lin,Ma Jun,Dai Jianping
Journal of neuro-oncology
Diffusion tensor imaging (DTI) has been proven to be a sophisticated and useful tool for the delineation of tumors. In the present study, we investigated the predictive role of DTI compared to other magnetic resonance imaging (MRI) techniques in combination with Ki-67 labeling index in defining tumor cell infiltration in the peritumoral regions of F98 glioma-bearing rats. A total of 29 tumor-bearing Fischer rats underwent T2-weighted imaging, contrast-enhanced T1-weighted imaging, and DTI of their brain using a 7.0-T MRI scanner. The fractional anisotropy (FA) ratios were correlated to the Ki-67 labeling index using the Spearman correlation analysis. A receiver operating characteristic curve (ROC) analysis was established to evaluate parameters with sensitivity and specificity in order to identify the threshold values for predicting tumor infiltration. Significant correlations were observed between the FA ratios and Ki-67 labeling index (r = - 0.865, p < 0.001). The ROC analysis demonstrated that the apparent diffusion coefficient (ADC) and FA ratios could predict 50% of the proliferating cells in the regions of interest (ROI), with a sensitivity of 88.1 and 81.3%, and a specificity of 86.2 and 90.2%, respectively (p < 0.001). Meanwhile, the two ratios could also predict 10% of the proliferating cells in the ROI, with a sensitivity of 82.5 and 94.9%, and a specificity of 100 and 88.9%, respectively (p < 0.001). The present study demonstrated that the FA ratios are closely correlated with the Ki-67 labeling index. Furthermore, both ADC and FA ratios, derived from DTI, were useful for quantitatively predicting the Ki-67 labeling of glioma cells.
Going Beyond Diffusion Tensor Imaging Tractography in Eloquent Glioma Surgery-High-Resolution Fiber Tractography: Q-Ball or Constrained Spherical Deconvolution?
Becker Daniela,Scherer Moritz,Neher Peter,Jungk Christine,Jesser Jessica,Pflüger Irada,Brinster Regina,Bendszus Martin,Bruckner Thomas,Maier-Hein Klaus,Unterberg Andreas
OBJECTIVE:As a result of the resolution of intravoxel fiber crossing, high-resolution fiber tractography (HRFT) provides advantages over conventional diffusion tensor imaging (DTI) for fiber tractography (FT). Nevertheless, neurosurgically applied FT is still predominantly based on DTI. Although the application of HRFT is evolving, there is still a lack of data about which method should be preferred. With this prospectively designed study, we present our initial experience comparing an analytical Q-ball imaging (QBI) approach with constrained spherical deconvolution (CSD) and conventional DTI-FT considering a particularly neurosurgical perspective. METHODS:For 18 patients with eloquent gliomas in the dominant hemisphere, probabilistic FT based on QBI, CSD, and DTI was performed for the major components of the language-associated pathways using a routine diffusion-weighted sequence. Quantitative analysis evaluated tract density, tract volume (TV), tract length (TL), number of fibers, and tract surface (TS) of the fiber object. RESULTS:Both HRFT models showed a significantly larger mean TV, TL, and TS compared with DTI (for QBI vs. DTI: TV (P = 0.0000), TL (P = 0.0048), and TS (P = 0.0129); for CSD vs. DTI: TV (P = 0.0000), TL (P = 0.0008), and TS (P = 0.0010)). However, results of QBI versus CSD did not differ significantly for these variables: TV (P = 0.1415), TL (P = 0.2837), and TS (P = 0.3692). Bland-Altman analysis supports these findings, suggesting systematically higher values for TV, TL, and TS with HRFT but no relevant differences of either QBI or CSD. Neither tumor volume nor peritumoral edema influenced FT results. CONCLUSIONS:Our quantitative analysis showed no significant differences regarding TV, TL, and TS for the HRFT methods; however, it suggested advantages over DTI-FT in terms of the display of marginal and terminal fibers. In our recently established setting, QBI-FT shows greater potential for integration into the clinical workflow.
Preoperative surgical planning of glioma: limitations and reliability of fMRI and DTI tractography.
Conti Nibali Marco,Rossi Marco,Sciortino Tommaso,Riva Marco,Gay Lorenzo G,Pessina Federico,Bello Lorenzo
Journal of neurosurgical sciences
Brain mapping techniques (intraoperative neurophysiology and neuropsychology) represent the gold standard in glioma surgery, and particularly in glioma resection. Since the introduction of MRI in the clinical practice, several advanced applications have been developed, like functional MRI (fMRI) and diffusion imaging-based tractography (DTI), which both have an application in glioma surgery. fMRI allows to identify cortical areas related to a specific function, DTI allows to reconstruct a model of the sub-cortical connectivity. This paper describes the clinical application of fMRI and DTI, enlightening sensitivity and specificity in comparison to gold standard and underlining their limitations in surgical decision making.
Molecular Subtype Classification in Lower-Grade Glioma with Accelerated DTI.
Aliotta E,Nourzadeh H,Batchala P P,Schiff D,Lopes M B,Druzgal J T,Mukherjee S,Patel S H
AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE:Image-based classification of lower-grade glioma molecular subtypes has substantial prognostic value. Diffusion tensor imaging has shown promise in lower-grade glioma subtyping but currently requires lengthy, nonstandard acquisitions. Our goal was to investigate lower-grade glioma classification using a machine learning technique that estimates fractional anisotropy from accelerated diffusion MR imaging scans containing only 3 diffusion-encoding directions. MATERIALS AND METHODS:Patients with lower-grade gliomas ( = 41) (World Health Organization grades II and III) with known () mutation and 1p/19q codeletion status were imaged preoperatively with DTI. Whole-tumor volumes were autodelineated using conventional anatomic MR imaging sequences. In addition to conventional ADC and fractional anisotropy reconstructions, fractional anisotropy estimates were computed from 3-direction DTI subsets using DiffNet, a neural network that directly computes fractional anisotropy from raw DTI data. Differences in whole-tumor ADC, fractional anisotropy, and estimated fractional anisotropy were assessed between -wild-type and -mutant lower-grade gliomas with and without 1p/19q codeletion. Multivariate classification models were developed using whole-tumor histogram and texture features from ADC, ADC + fractional anisotropy, and ADC + estimated fractional anisotropy to identify the added value provided by fractional anisotropy and estimated fractional anisotropy. RESULTS:ADC ( = .008), fractional anisotropy ( < .001), and estimated fractional anisotropy ( < .001) significantly differed between -wild-type and -mutant lower-grade gliomas. ADC ( < .001) significantly differed between -mutant gliomas with and without codeletion. ADC-only multivariate classification predicted mutation status with an area under the curve of 0.81 and codeletion status with an area under the curve of 0.83. Performance improved to area under the curve = 0.90/0.94 for the ADC + fractional anisotropy classification and to area under the curve = 0.89/0.89 for the ADC + estimated fractional anisotropy classification. CONCLUSIONS:Fractional anisotropy estimates made from accelerated 3-direction DTI scans add value in classifying lower-grade glioma molecular status.
Diffusion-Weighted Imaging and Diffusion Tensor Imaging for Differentiating High-Grade Glioma from Solitary Brain Metastasis: A Systematic Review and Meta-Analysis.
Suh C H,Kim H S,Jung S C,Kim S J
AJNR. American journal of neuroradiology
BACKGROUND:Accurate diagnosis of high-grade glioma and solitary brain metastasis is clinically important because it affects the patient's outcome and alters patient management. PURPOSE:To evaluate the diagnostic performance of DWI and DTI for differentiating high-grade glioma from solitary brain metastasis. DATA SOURCES:A literature search of Ovid MEDLINE and EMBASE was conducted up to November 10, 2017. STUDY SELECTION:Studies evaluating the diagnostic performance of DWI and DTI for differentiating high-grade glioma from solitary brain metastasis were selected. DATA ANALYSIS:Summary sensitivity and specificity were established by hierarchic logistic regression modeling. Multiple subgroup analyses were also performed. DATA SYNTHESIS:Fourteen studies with 1143 patients were included. The individual sensitivities and specificities of the 14 included studies showed a wide variation, ranging from 46.2% to 96.0% for sensitivity and 40.0% to 100.0% for specificity. The pooled sensitivity of both DWI and DTI was 79.8% (95% CI, 70.9%-86.4%), and the pooled specificity was 80.9% (95% CI, 75.1%-85.5%). The area under the hierarchical summary receiver operating characteristic curve was 0.87 (95% CI, 0.84-0.89). The multiple subgroup analyses also demonstrated similar diagnostic performances (sensitivities of 76.8%-84.7% and specificities of 79.7%-84.0%). There was some level of heterogeneity across the included studies (I = 36%); however, it did not reach a level of concern. LIMITATIONS:The included studies used various DWI and DTI parameters. CONCLUSIONS:DWI and DTI demonstrated a moderate diagnostic performance for differentiation of high-grade glioma from solitary brain metastasis.
Diagnostic Accuracy of PET Tracers for the Differentiation of Tumor Progression from Treatment-Related Changes in High-Grade Glioma: A Systematic Review and Metaanalysis.
de Zwart Paul L,van Dijken Bart R J,Holtman Gea A,Stormezand Gilles N,Dierckx Rudi A J O,Jan van Laar Peter,van der Hoorn Anouk
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. The systematic review included 39 studies (11 tracers). F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%-92%) and 84% (95% confidence interval, 69%-93%), respectively. -(2-F-fluoroethyl)-l-tyrosine (F-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%-95%) and specificity of 85% (95% confidence interval, 71%-93%). For -C-methyl)-l-methionine (C-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%-98%) and specificity was 82% (95% confidence interval, 68%-91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%-100% and 0%-100%, respectively, for F-FLT; 85%-100% and 72%-100%, respectively, for 3,4-dihydroxy-6-F-fluoro-l-phenylalanine (F-FDOPA); and 100% and 70%-88%, respectively, for C-choline. F-FET and C-MET, both amino-acid tracers, showed a comparably higher sensitivity than F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, F-FET and C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.
Quantitative magnetic resonance imaging and radiogenomic biomarkers for glioma characterisation: a systematic review.
Seow Pohchoo,Wong Jeannie Hsiu Ding,Ahmad-Annuar Azlina,Mahajan Abhishek,Abdullah Nor Aniza,Ramli Norlisah
The British journal of radiology
OBJECTIVE: :The diversity of tumour characteristics among glioma patients, even within same tumour grade, is a big challenge for disease outcome prediction. A possible approach for improved radiological imaging could come from combining information obtained at the molecular level. This review assembles recent evidence highlighting the value of using radiogenomic biomarkers to infer the underlying biology of gliomas and its correlation with imaging features. METHODS: :A literature search was done for articles published between 2002 and 2017 on Medline electronic databases. Of 249 titles identified, 38 fulfilled the inclusion criteria, with 14 articles related to quantifiable imaging parameters (heterogeneity, vascularity, diffusion, cell density, infiltrations, perfusion, and metabolite changes) and 24 articles relevant to molecular biomarkers linked to imaging. RESULTS: :Genes found to correlate with various imaging phenotypes were EGFR, MGMT, IDH1, VEGF, PDGF, TP53, and Ki-67. EGFR is the most studied gene related to imaging characteristics in the studies reviewed (41.7%), followed by MGMT (20.8%) and IDH1 (16.7%). A summary of the relationship amongst glioma morphology, gene expressions, imaging characteristics, prognosis and therapeutic response are presented. CONCLUSION::The use of radiogenomics can provide insights to understanding tumour biology and the underlying molecular pathways. Certain MRI characteristics that show strong correlations with EGFR, MGMT and IDH1 could be used as imaging biomarkers. Knowing the pathways involved in tumour progression and their associated imaging patterns may assist in diagnosis, prognosis and treatment management, while facilitating personalised medicine. ADVANCES IN KNOWLEDGE: :Radiogenomics can offer clinicians better insight into diagnosis, prognosis, and prediction of therapeutic responses of glioma.
Diagnostic Performance of Increased Signal Intensity Within the Resection Cavity on Fluid-Attenuated Inversion Recovery Sequences for Detection of Progression in Patients with Glioma.
Zhang Jing,Song Yanlin,He Min,Ren Qingqing,Zeng Yunhui,Liu Zhiyong,Liu Hao,Xu Jianguo
OBJECTIVE:To systematically evaluate the diagnostic performance of increased signal intensity within the resection cavity on fluid-attenuated inversion recovery (FLAIR) sequences for detection of progression in patients with glioma through performing a meta-analysis. METHODS:PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure were searched for potentially relevant literature. The study characteristics and relevant data were extracted. We estimated the pooled sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and diagnostic odds ratio and constructed summary receiver operating characteristics curves to identify the diagnostic value of FLAIR signal increase for detection of glioma progression. RESULTS:A total of 4 studies with 438 patients were included. The pooled sensitivity and specificity of increased signal intensity in FLAIR sequences in the resection cavity for detection of glioma progression were 0.36 (95% confidence interval 0.31-0.42) and 0.93 (95% confidence interval 0.86-0.97), respectively. The area under the curve was 0.7505. Subgroup analyses also were performed according to different patient sources, tumor grades, and definitions of progression. No significant publication bias was found in the meta-analysis (P = 0.85). CONCLUSIONS:Our results suggested that increased signal intensity within the resection cavity on FLAIR sequences could indicate tumor progression early with high specificity in patients with glioma. This readily accessible sign could implicate closer monitoring and could be crucial for therapeutic decisions and outcome. However, because of the limited number of studies, more well-designed studies are warranted to further verify our results and elucidate the underlining mechanisms.
How much is enough-Can resting state fMRI provide a demarcation for neurosurgical resection in glioma?
Ghinda Diana C,Wu Jin-Song,Duncan Niall W,Northoff Georg
Neuroscience and biobehavioral reviews
This study represents a systematic review of the insights provided by resting state functional MRI (rs-fMRI) use in the glioma population. Following PRISMA guidelines, 45 studies were included in the review and were classified in glioma-related neuronal changes (n=28) and eloquent area localization (n=17). Despite the heterogeneous nature of the studies, there is considerable evidence of diffuse functional reorganization occurring in the setting of gliomas with local and interhemispheric functional connectivity alterations involving different functional networks. The studies showed evidence of decreased long distance functional connectivity and increased global local efficiency occurring in the setting of gliomas. The tumour grade seems to correlate with distinct functional connectivity changes. Overall, there is a potential clinical utility of rs-fMRI for identifying the functional brain network disruptions occurring in the setting of gliomas. Further studies utilizing standardized analytical methods are required to elucidate the mechanism through which gliomas induce global changes in brain connectivity.
Genetic Polymorphisms of CCDC26 rs891835, rs6470745, and rs55705857 in Glioma Risk: A Systematic Review and Meta-analysis.
González-Castro Thelma Beatriz,Juárez-Rojop Isela Esther,López-Narváez María Lilia,Tovilla-Zárate Carlos Alfonso,Genis-Mendoza Alma Delia,Pérez-Hernández Nonazit,Martínez-Magaña José Jaime,Rodríguez-Pérez José Manuel
A genetic component is accepted in the etiology of the glioma. Evidence from candidate genes studies and GWAS reveal that CCDC26 gene could increase the risk of glioma. We performed a systematic review and up-to-date meta-analysis to explore if polymorphisms of CCDC26 gene (rs891835, rs6470745, and rs55705857) may be a susceptibility factor in developing glioma. An online search in PubMed, Web of Science, and SCOPUS up to September 2018 was performed. The pooled odds ratios were evaluated by fixed effects model and random effects model. Analyses of the overall sample and ethnic sub-groups were performed. In all the analyses, the allelic, additive, dominant, and recessive models were used. We found an association between all polymorphisms evaluated and an increased risk for glioma in the overall population in all the models studied. In sub-group analysis, we found that rs891835 and rs6470745 increased the risk of glioma in Europeans and Caucasians. On the other hand, the rs891835 polymorphism did not reveal any statistical association in Chinese population. Taken into consideration the limitations of this study, the present findings suggest a possible participation of rs891835, rs6470745, and rs55705857 as risk factors to develop glioma. Furthermore, it is possible that the involvement of CCDC26 variants depends on ethnicity. However, we recommend to perform further studies to have conclusive outcomes.
IDH1 mutation is associated with a higher preoperative seizure incidence in low-grade glioma: A systematic review and meta-analysis.
Li Yucai,Shan Xia,Wu Zhifeng,Wang Yinyan,Ling Miao,Fan Xing
PURPOSE:Gliomas, particularly low-grade gliomas (LGGs), are highly epileptogenic. Seizure is the most common presenting sign of LGG patients and significantly decreases their quality of life. Accordingly, there is a need for a better understanding of the mechanisms and risk factors of glioma-related epilepsy. The current study aimed to perform a comprehensive meta-analysis to investigate the correlation of isocitrate-dehydrogenase 1 (IDH1), an important molecular biomarker for glioma classification and prognosis, to preoperative seizure incidence in LGG. METHODS:PUBMED, EMBASE, and Web of Science databases were searched for relevant studies. The odds ratio (OR) and corresponding 95% confidence interval (CI) were used as the primary measures to assess the correlation between IDH1 mutation and preoperative seizure incidence. RESULTS:A total of 722 LGG patients, including 555 patients with IDH1 mutation and 167 patients with wild-type IDH1 were enrolled in the current meta-analysis. The pooled OR was 2.47 (95% CI 1.70-3.57, Z = 4.78, p < 0.01). No significant heterogeneity was observed among all included studies and no publication bias was identified. CONCLUSION:The current meta-analysis identified that IDH1 mutation was correlated to a higher preoperative seizure incidence in LGG. This result would generate impetus for research on the mechanisms behind this correlation, and provide a new idea for the individualized treatment of glioma-related epilepsy.
Extent of Resection in Glioma-A Review of the Cutting Edge.
D'Amico Randy S,Englander Zachary K,Canoll Peter,Bruce Jeffrey N
Modern glioma surgery has evolved from the principal belief that safe, maximal tumor resection improves symptom management, quality of life, progression-free survival, and overall survival in both low-grade and high-grade glioma. However, in the absence of level I data, the overwhelming support for this idea is derived largely from retrospective series. As a result, the influence of increasing extent of resection and reducing tumor burden on the efficacy of postoperative chemotherapy and radiotherapy, and survival, remains inadequately defined. This situation is particularly true because gliomas represent a widely heterogeneous group of tumors with varying behaviors and prognoses rooted in their complex molecular profile. The neurosurgical community has made a large effort to define the clinical benefits of maximizing tumor resection, with particular attention paid to the ever-evolving understanding of glioma molecular heterogeneity. Important new technologies have been developed concurrently to mitigate neurologic risks related to the pursuit of maximizing extent of resection. These advances reflect the modern goal of glioma surgery to find the optimal balance between tumor removal and neurologic compromise. We review the current literature supporting safe, maximal resection for gliomas.
Perfusion MRI as a diagnostic biomarker for differentiating glioma from brain metastasis: a systematic review and meta-analysis.
Suh Chong Hyun,Kim Ho Sung,Jung Seung Chai,Choi Choong Gon,Kim Sang Joon
OBJECTIVES:Differentiation of glioma from brain metastasis is clinically crucial because it affects the clinical outcome of patients and alters patient management. Here, we present a systematic review and meta-analysis of the currently available data on perfusion magnetic resonance imaging (MRI) for differentiating glioma from brain metastasis, assessing MRI protocols and parameters. METHODS:A computerised search of Ovid-MEDLINE and EMBASE databases was performed up to 3 October 2017, to find studies on the diagnostic performance of perfusion MRI for differentiating glioma from brain metastasis. Pooled summary estimates of sensitivity and specificity were obtained using hierarchical logistic regression modelling. We conducted meta-regression and subgroup analyses to explain the effects of the study heterogeneity. RESULTS:Eighteen studies with 900 patients were included. The pooled sensitivity and specificity were 90% (95% CI, 84-94%) and 91% (95% CI, 84-95%), respectively. The area under the hierarchical summary receiver operating characteristic curve was 0.96 (95% CI, 0.94-0.98). The meta-regression showed that the percentage of glioma in the study population and the study design were significant factors affecting study heterogeneity. In a subgroup analysis including patients with glioblastoma only, the pooled sensitivity was 92% (95% CI, 84-97%) and the pooled specificity was 94% (95% CI, 85-98%). CONCLUSIONS:Although various perfusion MRI techniques were used, the current evidence supports the use of perfusion MRI to differentiate glioma from brain metastasis. In particular, perfusion MRI showed excellent diagnostic performance for differentiating glioblastoma from brain metastasis. KEY POINTS:• Perfusion MRI shows high diagnostic performance for differentiating glioma from brain metastasis. • The pooled sensitivity was 90% and pooled specificity was 91%. • Peritumoral rCBV derived from DSC is a relatively well-validated.
Prevalence of symptoms in glioma patients throughout the disease trajectory: a systematic review.
IJzerman-Korevaar Margriet,Snijders Tom J,de Graeff Alexander,Teunissen Saskia C C M,de Vos Filip Y F
Journal of neuro-oncology
BACKGROUND:Glioma patients suffer from a wide range of symptoms which influence quality of life negatively. The aim of this review is to give an overview of symptoms most prevalent in glioma patients throughout the total disease trajectory, to be used as a basis for the development of a specific glioma Patient Reported Outcome Measure (PROM) for early assessment and monitoring of symptoms in glioma patients. METHODS:A systematic review focused on symptom prevalence in glioma patients in different phases of disease and treatment was performed in MEDLINE, CINAHL and EMBASE according to PRISMA recommendations. We calculated weighted means for prevalence rates per symptom. RESULTS:The search identified 2.074 unique papers, of which 32 were included in this review. In total 25 symptoms were identified. The ten most prevalent symptoms were: seizures (37%), cognitive deficits (36%), drowsiness (35%), dysphagia (30%), headache (27%), confusion (27%), aphasia (24%), motor deficits (21%), fatigue (20%) and dyspnea (20%). CONCLUSIONS:Eight out of ten of the most prevalent symptoms in glioma patients are related to the central nervous system and therefore specific for glioma. Our findings emphasize the importance of tailored symptom care for glioma patients and may aid in the development of specific PROMs for glioma patients in different phases of the disease.
Association Between IDH1 and IDH2 Mutations and Preoperative Seizures in Patients with Low-Grade Versus High-Grade Glioma: A Systematic Review and Meta-Analysis.
Phan Kevin,Ng Wyatt,Lu Victor M,McDonald Kerrie L,Fairhall Jacob,Reddy Rajesh,Wilson Peter
BACKGROUND:Patients with brain tumors, particularly gliomas, commonly present with seizures. Higher incidence of seizure has been reported in low-grade gliomas and tumors located within the temporal and insular area. The association between IDH1 and IDH2 mutations with preoperative seizures in glioma and the magnitude of this association in low-grade versus high-grade gliomas are unclear. To clarify this relationship, a systematic review and meta-analysis was performed. METHODS:Following accepted guidelines and systematic review recommendations, electronic searches were performed in journal databases up to May 2017. Data were extracted and pooled via meta-analysis. RESULTS:We compared 782 patients with IDH1 and IDH2 mutations with 803 patients with wild-type IDH1 and IDH2 before surgery. There was a significant difference in seizure incidence between the IDH1 mutation group (61.6%) and wild-type IDH1 group (32.1%) (odds ratio 2.76; 95% confidence interval, 1.26-6.02; I = 73%; P = 0.01). Similar findings were observed in analysis of IDH1 and IDH2 mutations (odds ratio 2.74; 95% confidence interval, 1.74-4.33; I = 58%; P < 0.0001). The difference remained in both mutation groups (IDH1, IDH1 and IDH2) with grade II gliomas but not with grade III and IV gliomas. Patients with grade II gliomas showed a higher rate of IDH1 and IDH2 mutations and seizures than patients with grade III and IV gliomas. CONCLUSIONS:This study demonstrated a significant association of IDH1 and IDH2 mutations with incidence of preoperative seizures. This association was significant only in patients with low-grade glioma (grade II) and not in patients with higher grade gliomas (grade III and IV).
Preoperative grading of supratentorial gliomas using high or standard b-value diffusion-weighted MR imaging at 3T.
Cihangiroglu M M,Ozturk-Isik E,Firat Z,Kilickesmez O,Ulug A M,Ture U
Diagnostic and interventional imaging
PURPOSE:The goal of this study was to compare diffusion-weighted magnetic resonance imaging (DW-MRI) using high b-value (b=3000s/mm) to DW-MRI using standard b-value (b=1000s/mm) in the preoperative grading of supratentorial gliomas. MATERIALS AND METHODS:Fifty-three patients with glioma had brain DW-MRI at 3T using two different b-values (b=1000s/mm and b=3000s/mm). There were 35 men and 18 women with a mean age of 40.5±17.1 years (range: 18-79 years). Mean, minimum, maximum, and range of apparent diffusion coefficient (ADC) values for solid tumor ROIs (ADC, ADC, ADC, and ADC), and the normalized ADC (ADC) were calculated. A Kruskal-Wallis statistic with Bonferroni correction for multiple comparisons was applied to detect significant ADC parameter differences between tumor grades by including or excluding 19 patients with an oligodendroglioma. Receiver operating characteristic curve analysis was conducted to define appropriate cutoff values for grading gliomas. RESULTS:No differences in ADC derived parameters were found between grade II and grade III gliomas. Mean ADC values using standard b-value were 1.17±0.27×10mm/s [range: 0.63-1.61], 1.05±0.22×10mm/s [range: 0.73-1.33], and 0.86±0.23×10mm/s [range: 0.52-1.46] for grades II, III and IV gliomas, respectively. Using high b-value, mean ADC values were 0.89±0.24×10mm/s [range: 0.42-1.25], 0.82±0.20×10mm/s [range: 0.56-1.10], and 0.59±0.17×10mm/s [range: 0.40-1.01] for grades II, III and IV gliomas, respectively. ADC, ADC, ADC, and ADC were different between grade II and grade IV gliomas at both standard and high b-values. Differences in ADC, ADC, and ADC were found between grade III and grade IV only using high b-value. CONCLUSION:ADC parameters derived from DW-MRI using a high b-value allows a better differential diagnosis of gliomas, especially for differentiating grades III and IV, than those derived from DW-MRI using a standard b-value.
Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas.
Schön S,Cabello J,Liesche-Starnecker F,Molina-Romero M,Eichinger P,Metz M,Karimov I,Preibisch C,Keupp J,Hock A,Meyer B,Weber W,Zimmer C,Pyka T,Yakushev I,Gempt J,Wiestler B
European journal of nuclear medicine and molecular imaging
PURPOSE:Imaging glioma biology holds great promise to unravel the complex nature of these tumors. Besides well-established imaging techniques such O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging, amide proton transfer-weighted (APTw) imaging has emerged as a promising novel MR technique. In this study, we aimed to better understand the relation between these imaging biomarkers and how well they capture cellularity and vascularity in newly diagnosed gliomas. METHODS:Preoperative MRI and FET-PET data of 46 patients (31 glioblastoma and 15 lower-grade glioma) were segmented into contrast-enhancing and FLAIR-hyperintense areas. Using established cutoffs, we calculated hot-spot volumes (HSV) and their spatial overlap. We further investigated APTw and CBV values in FET-HSV. In a subset of 10 glioblastoma patients, we compared cellularity and vascularization in 34 stereotactically targeted biopsies with imaging. RESULTS:In glioblastomas, the largest HSV was found for APTw, followed by PET and CBV (p < 0.05). In lower-grade gliomas, APTw-HSV was clearly lower than in glioblastomas. The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions. APTw correlated significantly with cellularity, similar to FET, while the association with vascularity was more pronounced in CBV and FET. CONCLUSIONS:We found a relevant spatial overlap in glioblastomas between hotspots of APTw and FET both in contrast-enhancing and FLAIR-hyperintense tumor. As suggested by earlier studies, APTw was lower in lower-grade gliomas compared with glioblastomas. APTw meaningfully contributes to biological imaging of gliomas.
Advanced imaging parameters improve the prediction of diffuse lower-grade gliomas subtype, IDH mutant with no 1p19q codeletion: added value to the T2/FLAIR mismatch sign.
Lee Min Kyoung,Park Ji Eun,Jo Youngheun,Park Seo Young,Kim Sang Joon,Kim Ho Sung
OBJECTIVES:A combination of T2/FLAIR mismatch sign and advanced imaging parameters may improve the determination of molecular subtypes of diffuse lower-grade glioma. We assessed the diagnostic value of adding the apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) to the T2/FLAIR mismatch sign for differentiation of the IDH mutation or 1p/19q codeletion. MATERIALS AND METHODS:Preoperative conventional, diffusion-weighted, and dynamic susceptibility contrast imaging were performed on 110 patients with diffuse lower-grade gliomas. The study population was classified into three groups using molecular subtype, namely IDH mutation and 1p/19q codeletion (IDHmut-Codel), IDH wild type (IDHwt) and IDH mutation and no 1p/19q codeletion (IDHmut-Noncodel). T2/FLAIR mismatch sign and the histogram parameters of apparent diffusion coefficient (ADC) and normalised cerebral blood volume (nCBV) values were assessed. A multivariate logistic regression model was constructed to distinguish IDHmut-Noncodel from IDHmut-Codel and IDHwt and from IDHwt, and the performance was compared with that of single parameters using the area under the receiver operating characteristics curve (AUC). RESULTS:Positive visual T2/FLAIR mismatch sign and higher nCBV skewness were significant variables to distinguish IDHmut-Noncodel from the other two groups (AUC, 0.88; 95% CI, 0.81-0.96). A lower ADC10 was a significant variable for distinguishing IDHmut-Noncodel from the IDHwt group (AUC, 0.75; 95% CI, 0.62-0.89). Adding ADC or CBV histogram parameters to T2/FLAIR mismatch sign improved performance in distinguishing IDHmut-Noncodel from the other two groups (AUC 0.882 vs. AUC 0.810) or from IDHwt (AUC 0.923 vs. AUC 0.868). CONCLUSIONS:The combination of the T2/FLAIR mismatch sign with ADC or CBV histogram parameters can improve the identification of IDHmut-Noncodel diffuse lower-grade gliomas, which can be easily applied in clinical practice. KEY POINTS:• The combination of the T2/FLAIR mismatch sign with the ADC or CBV histogram parameters can improve the identification of IDHmut-Noncodel diffuse lower-grade gliomas. • The multivariable model showed a significantly better performance for distinguishing the IDHmut-Noncodel group from other diffuse lower-grade gliomas than the T2/FLAIR mismatch sign alone or any single parameter. • The IDHmut-Noncodel type was associated with intermediate treatment outcomes; therefore, the identification of IDHmut-Noncodel diffuse lower-grade gliomas could be helpful for determining the clinical approach.
Predicting Genotype and Survival in Glioma Using Standard Clinical MR Imaging Apparent Diffusion Coefficient Images: A Pilot Study from The Cancer Genome Atlas.
Wu C-C,Jain R,Radmanesh A,Poisson L M,Guo W-Y,Zagzag D,Snuderl M,Placantonakis D G,Golfinos J,Chi A S
AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE:Few studies have shown MR imaging features and ADC correlating with molecular markers and survival in patients with glioma. Our purpose was to correlate MR imaging features and ADC with molecular subtyping and survival in adult diffuse gliomas. MATERIALS AND METHODS:Presurgical MRIs and ADC maps of 131 patients with diffuse gliomas and available molecular and survival data from The Cancer Genome Atlas were reviewed. MR imaging features, ADC (obtained by ROIs within the lowest ADC area), and mean relative ADC values were evaluated to predict () mutation, 1p/19q codeletion status, promoter methylation, and overall survival. RESULTS: wild-type gliomas tended to exhibit enhancement, necrosis, and edema; >50% enhancing area ( < .001); absence of a cystic area ( = .013); and lower mean relative ADC (median, 1.1 versus 1.6; < .001) than -mutant gliomas. By means of a cutoff value of 1.08 for mean relative ADC, -mutant and wild-type gliomas with lower mean relative ADC (<1.08) had poorer survival than those with higher mean relative ADC (median survival time, 24.2 months; 95% CI, 0.0-54.9 months versus 62.0 months; = .003; and median survival time, 10.4 months; 95% CI, 4.4-16.4 months versus 17.7 months; 95% CI, 11.6-23.7 months; = .041, respectively), regardless of World Health Organization grade. Median survival of those with -mutant glioma with low mean relative ADC was not significantly different from that in those with wild-type glioma. Other MR imaging features were not statistically significant predictors of survival. CONCLUSIONS: wild-type glioma showed lower ADC values, which also correlated with poor survival in both -mutant and wild-type gliomas, irrespective of histologic grade. A subgroup with -mutant gliomas with lower ADC had dismal survival similar to that of those with wild-type gliomas.
Glioma infiltration sign on high b-value diffusion-weighted imaging in gliomas and its prognostic value.
Zeng Qiang,Ling Chenhan,Shi Feina,Dong Fei,Jiang Biao,Zhang Jianmin
Journal of magnetic resonance imaging : JMRI
BACKGROUND:Glioma cells may infiltrate beyond the tumor margins revealed on conventional structural images. PURPOSE:To investigate whether the presence of a glioma infiltration sign on high b-value diffusion-weighted imaging (DWI) can predict the prognosis of gliomas. STUDY TYPE:Retrospective cohort. SUBJECTS:Fifty-two patients with gliomas (14 WHO grade II; 13 WHO grade III; 25 WHO grade IV). FIELD STRENGTH/SEQUENCE:3.0T, including a T -weighted contrast-enhanced (T w-CE) sequence, contrast-enhanced T -flair sequence, and a DWI sequence. ASSESSMENT:T w-CE images and contrast-enhanced T -flair images were used for identifying the tumor region for enhancing and nonenhancing gliomas, respectively. The glioma infiltration sign was defined as the presence of a peritumoral abnormal high signal region on DWI map, which was adjacent to the tumor region and had higher signal than surrounding areas. This sign was assessed on a high b-value DWI map with b = 3000 s/mm . For patients with glioma infiltration sign, DWI3000 , DWI1000 , ADC3000 , and ADC1000 were measured by drawing a region of interest over the peritumoral abnormal high signal region. STATISTICAL TESTS:Survival analysis was conducted by using Cox regression. RESULTS:Glioma infiltration sign was observed in 28 (53.8%) patients. The occurrence rate of this sign was 92.0% in grade IV gliomas, 30.8% in grade III gliomas, and 7.1% in grade II gliomas. The glioma infiltration sign could independently predict both the progression-free survival (hazard ratio [HR], 95% confidence interval [CI] = 8.58 [3.19-23.03], P < 0.001) and overall survival (HR, 95% CI = 11.90 [3.41-41.55], P < 0.001) after adjustment. For patients with glioma infiltration sign, DWI3000 (P = 0.005) and ADC3000 (P = 0.008) were both independent predictors of overall survival after adjustment, while DWI1000 and ADC1000 were not. DATA CONCLUSION:The glioma infiltration sign on high b-value DWI is an independent predictor of poor prognosis in glioma patients. High b-value DWI might be a convenient method to detect glioma infiltration. LEVEL OF EVIDENCE:3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
The relationship between Cho/NAA and glioma metabolism: implementation for margin delineation of cerebral gliomas.
Guo Jun,Yao Chengjun,Chen Hong,Zhuang Dongxiao,Tang Weijun,Ren Guang,Wang Yin,Wu Jinsong,Huang Fengping,Zhou Liangfu
BACKGROUND:The marginal delineation of gliomas cannot be defined by conventional imaging due to their infiltrative growth pattern. Here we investigate the relationship between changes in glioma metabolism by proton magnetic resonance spectroscopic imaging ((1)H-MRSI) and histopathological findings in order to determine an optimal threshold value of choline/N-acetyl-aspartate (Cho/NAA) that can be used to define the extent of glioma spread. METHOD:Eighteen patients with different grades of glioma were examined using (1)H-MRSI. Needle biopsies were performed under the guidance of neuronavigation prior to craniotomy. Intraoperative magnetic resonance imaging (MRI) was performed to evaluate the accuracy of sampling. Haematoxylin and eosin, and immunohistochemical staining with IDH1, MIB-1, p53, CD34 and glial fibrillary acidic protein (GFAP) antibodies were performed on all samples. Logistic regression analysis was used to determine the relationship between Cho/NAA and MIB-1, p53, CD34, and the degree of tumour infiltration. The clinical threshold ratio distinguishing tumour tissue in high-grade (grades III and IV) glioma (HGG) and low-grade (grade II) glioma (LGG) was calculated. RESULTS:In HGG, higher Cho/NAA ratios were associated with a greater probability of higher MIB-1 counts, stronger CD34 expression, and tumour infiltration. Ratio threshold values of 0.5, 1.0, 1.5 and 2.0 appeared to predict the specimens containing the tumour with respective probabilities of 0.38, 0.60, 0.79, 0.90 in HGG and 0.16, 0.39, 0.67, 0.87 in LGG. CONCLUSIONS:HGG and LGG exhibit different spectroscopic patterns. Using (1)H-MRSI to guide the extent of resection has the potential to improve the clinical outcome of glioma surgery.