OBJECTIVE: Our study aimed to examine and contrast the clinical and radiological characteristics of TDL, high-grade gliomas (HGG) and primary CNS lymphoma (CNSL).
METHOD: This was a retrospective review of 66 patients (23 TDL, 31 HGG and 12 CNSL). Clinical and laboratory data were obtained. MRI brain at presentation were analyzed by two independent, blinded neuroradiologists.
RESULTS: Patients with TDLs were younger and predominantly female. Sensorimotor deficits and ataxia were more common amongst TDL whereas headaches and altered mental status were associated with HGG and CNSL. Compared to HGG and CNSL, MRI characteristics supporting TDL included relatively smaller size, lack of or mild mass effect, incomplete peripheral rim enhancement, absence of central enhancement or restricted diffusion, lack of cortical involvement, and presence of remote white matter lesions on the index scan. Paradoxically, some TDLs may present atypically or radiologically mimic CNS lymphomas.
CONCLUSION: Careful evaluation of clinical and radiological features helps in differentiating TDLs at first presentation from CNS neoplasms.
MATERIALS AND METHODS: The study was conducted with tumor samples from patients diagnosed with glioblastoma (Grade IV). To create spheroids, primary cultures were isolated from tumor tissue samples; the said cultures were characterized morphologically and immunocytochemically, and then planted into round-bottom ultra low-adhesion plates. The number of cells for planting was chosen empirically. The characteristics of the growth of cell cultures were compared with spheroids from glioblastomas of patients with U373 MG stable line of human glioblastoma. Visualization of autofluorescence of metabolic coenzymes of nicotinamide adenine dinucleotide (phosphate) NAD(P)H and flavin adenine dinucleotide (FAD) in spheroids was performed by means of an LSM 880 laser scanning microscope (Carl Zeiss, Germany) with a FLIM module (Becker & Hickl GmbH, Germany). The autofluorescence decay parameters were studied under normoxic and hypoxic conditions (3.5% О2).
RESULTS: An original protocol for 3D glioblastoma spheroids cultivation was developed. Primary glial cultures from surgical material of patients were obtained and characterized. The isolated glioblastoma cells had a spindle-shaped morphology with numerous processes and a pronounced granularity of cytoplasm. All cultures expressed glial fibrillary acidic protein (GFAP). The optimal seeding dose of 2000 cells per well was specified; its application results in formation of spheroids with a dense structure and stable growth during 7 days. The FLIM method helped to establish that spheroid cells from the patient material had a generally similar metabolism to spheroids from the stable line, however, they demonstrated more pronounced metabolic heterogeneity. Cultivation of spheroids under hypoxic conditions revealed a transition to a more glycolytic type of metabolism, which is expressed in an increase in the contribution of the free form of NAD(P)H to fluorescence decay.
CONCLUSION: The developed model of tumor spheroids from patients' glioblastomas in combination with the FLIM can serve as a tool to study characteristics of tumor metabolism and develop predictive tests to evaluate the effectiveness of antitumor therapy.
METHODS: A total of 74 patients with histologically proven HGGs treated between January 2008 and December 2014, who fulfilled the inclusion criteria, were enrolled. Kaplan-Meier survival estimates and Cox proportional hazard regression were used.
RESULTS: Significant longer survival time (months) was observed in the FG group compared with the conventional group (12 months versus 8 months, P < 0.020). Even without adjuvant therapy, HGG patients from FG group survived longer than those from the conventional group (8 months versus 3 months, P = 0.006). No significant differences were seen in postoperative Karnofsky performance scale (KPS) between the groups at 6 weeks and 6 months after surgery compared to pre-operative KPS. Cox proportional hazard regression identified four independent predictors of survival: KPS > 80 (P = 0.010), histology (P < 0.001), surgical method (P < 0.001) and adjuvant therapy (P < 0.001).
CONCLUSION: This study showed a significant clinical benefit for HGG patients in terms of overall survival using FG surgery as it did not result in worsening of post-operative function outcome when compared with the conventional surgical method. We advocate a further multicentered, randomised controlled trial to support these findings before FG surgery can be implemented as a standard surgical adjunct in local practice for the benefit of HGG patients.
Methods: Forty histologically proven glioma patients underwent a standard MRI tumour protocol with the addition of IOP sequence. The regions of tumour (solid enhancing, solid non-enhancing, and cystic regions) were delineated using snake model (ITK-SNAP) with reference to structural and diffusion MRI images. The lipid distribution map was constructed based on signal loss ratio (SLR) obtained from the IOP imaging. The mean SLR values of the regions were computed and compared across the different glioma grades.
Results: The solid enhancing region of glioma had the highest SLR for both Grade II and III. The mean SLR of solid non-enhancing region of tumour demonstrated statistically significant difference between the WHO grades (grades II, III & IV) (mean SLRII = 0.04, mean SLRIII = 0.06, mean SLRIV = 0.08, & p glioma. This technique adds to the surgical diagnostic yield by identifying biopsy targets. It can also be used as an adjunct grading tool for glioma as well as to provide information about lipidomics landscape in glioma development.
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.
METHODS: A phantom study was performed to investigate the correlation of (1)H MRS-visible lipids with the signal loss ratio (SLR) obtained using IOP imaging. A cross-sectional study approved by the institutional review board was carried out in 22 patients with different glioma grades. The patients underwent scanning using IOP imaging and single-voxel spectroscopy (SVS) using 3T MRI. The brain spectra acquisitions from solid and cystic components were obtained and correlated with the SLR for different grades.
RESULTS: The phantom study showed a positive linear correlation between lipid quantification at 0.9 parts per million (ppm) and 1.3 ppm with SLR (r = 0.79-0.99, p glioma grades using optimal cut-points of 0.064 and 0.086 with classification probabilities for grade II (SII = 1), grade III (SIII = 0.50) and grade IV (SIV = 0.89).
CONCLUSIONS: The results underscore the lipid quantification differences in grades of glioma and provide a more comprehensive characterization by using SLR in chemical shift GE IOP imaging. SLR in IOP sequence demonstrates good performance in glioma grading.
KEY POINTS: • Strong correlation was seen between lipid concentration and SLR obtained using IOP • IOP sequence demonstrates significant differences in signal loss within the glioma grades • SLR at solid tumour portions was the best measure for differentiation • This sequence is applicable in a research capacity for glioma staging armamentarium.