Takeshi Takayasu

Lymphomas and glioblastomas: Differences in the apparent diffusion coefficient evaluated with high b-value diffusion-weighted magnetic resonance imaging at 3 T

BACKGROUND AND PURPOSE As the usefulness of the apparent diffusion coefficient (ADC) obtained from diffusion-weighted images (DWI) for the differential diagnosis between glioblastoma and primary central nervous system lymphoma is controversial, we assessed whether high b-value DWI at b 4000 s/mm(2) could discriminate between glioblastoma and lymphoma. We also compared the power of high- and standard b-value (b-4000, b-1000) imaging on a 3-Tesla (3T) magnetic resonance (MR) instrument. MATERIALS AND METHODS This study was approved by our Institutional Review Board. We acquired DWI at 3T with b = 1000 and b = 4000 s/mm(2) in 10 patients with lymphoma and 14 patients with glioblastoma. The ADC was measured by placing multiple regions of interest (ROI) on ADC maps of the site of enhanced lesions on contrast-enhanced T1-weighted MR images. We avoided hemorrhagic and cystic lesions by using T1-, T2-, FLAIR-, and T2* MR images. The ADC values of each tumor were determined preoperatively from several ROI and expressed as the minimum-, mean-, and maximum ADC value (ADC(MIN), ADC(MEAN), ADC(MAX)). We evaluated the relationship between ADCs and histological information including tumor cellularity. RESULTS All ADC values were statistically associated with tumor cellularity. ADC(MIN) at b-4000 was associated with tumor cellularity more significantly than ADC(MIN) at b-1000. All ADC values were lower for lymphoma than glioblastoma and the statistical difference was larger at b = 4000- than b = 1000 s/mm(2). According to the results of discriminant analysis, the log likelihood was greatest for ADC(MIN) at b = 4000. At a cut-off value of ADC(MIN) = 0.500 × 10(-3)mm(2)/s at b-4000 it was possible to differentiate between lymphoma and glioblastoma (sensitivity 90.9%, specificity 91.7%). CONCLUSIONS Calculating the ADC value is useful for distinguishing lymphoma from glioblastoma. The lowest degree of overlapping and a better inverse correspondence with tumor cellularity were obtained with ADC(MIN) at b-4000 s/mm(2) at 3T MRI.

Preoperative histological grading of meningiomas using apparent diffusion coefficient at 3T MRI

PURPOSE We assessed whether a high b-value DWI at b=4000s/mm(2) would discriminate the histopathological differentiation of the tumor grade of meningiomas, and also focused on the relationship between radiologic features and the tumor grade. MATERIALS AND METHODS We acquired DWI at 3T with b=1000 and b=4000s/mm(2) in 77 patients (42, 31 and 4 patients were WHO grades I (G1), II (G2), and III (G3), respectively). The apparent diffusion coefficient (ADC) was measured by placing multiple regions of interest (ROIs) on ADC maps. The ADC values of each tumor were determined preoperatively from several ROIs, and expressed as the minimum (ADCMIN), mean (ADCMEAN), and maximum absolute values (ADCMAX). We evaluated the relationship between ADCs and histological findings, and assessed the radiologic features such as tumor location, tumor size, presence/absence of peritumoral edema, shape of the tumor, presence/absence of bone destruction or hyperplasia, status of contrast enhancement, presence/absence of calcification and cyst. RESULTS ADCs of the meningiomas were inversely correlated with the histological grade of meningiomas. According to results of the discriminant analysis, the apparent log likelihood value was greatest for ADCMIN at b=4000. Furthermore, only the ADCMIN value at b=4000 was significantly correlated with the histological grade of meningiomas when we performed a multiple logistic regression analysis to identify the significant independent factors such as shape of tumor, presence/absence of bone destruction, status of contrast enhancement, presence/absence of cyst and ADCMIN at b=4000. CONCLUSION A meningioma with a low ADCMIN at a high b-value might imply a high-grade meningioma.

Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment

BACKGROUND The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. MATERIALS AND METHODS Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6-65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan-Meier survival curves (log-rank test). RESULTS It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. DISCUSSION AND CONCLUSION High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab.

A pituitary abscess showing high signal intensity on diffusion-weighted imaging.

The utility of diffusion-weighted imaging (DWI) for the diagnosis of intracranial abscesses has already been established. However, the use of DWI for pituitary abscesses has not been previously reported. We present a case of postoperative pituitary abscess in which T1-weighted and T2-weighted magnetic resonance imaging (MRI) revealed a supra-sellar cystic mass, with the cyst contents showing high intensity on DWI. This case suggests that DWI is useful for the diagnosis of pituitary abscesses.

Magnetic resonance spectroscopy detection of high lipid levels in intraaxial tumors without central necrosis: a characteristic of malignant lymphoma.

OBJECT The differentiation of malignant lymphomas from gliomas or malignant gliomas by conventional MRI can be difficult. The authors studied Gd-enhanced MR images to obtain a differential diagnosis between malignant lymphomas and gliomas without central necrosis or cystic changes and investigated the diagnostic value of single-voxel proton MR spectroscopy ((1)H-MRS) using different parameters, including lipid levels. METHODS This was a retrospective study of patients with primary malignant CNS lymphoma (n = 17) and glioma (n = 122 [Grades I, II, III, and IV in 10, 30, 33, and 49 patients, respectively]) who were treated between 2007 and 2013. The authors focused on 15 patients with homogeneously enhanced primary malignant CNS lymphomas and 7 homogeneously enhanced gliomas. Images of all the included tumors were acquired with (1)H-MRS at 3 T, and the diagnoses were histologically confirmed. RESULTS Using a short echo time (1)H-MRS, large lipid peaks were observed in all 17 patients with a malignant lymphoma, in 39 patients (79.6%) with a Grade IV glioma, and in 10 patients (30.3%) with a Grade III glioma. A focus on homogeneously enhanced tumors revealed large lipid peaks in 15 malignant lymphomas that were free of central necrosis on Gd-enhanced T1-weighted images. Conversely, in the 7 homogeneously enhanced gliomas (glioblastoma and anaplastic astrocytoma, n = 2 each; anaplastic oligodendroglioma, diffuse astrocytoma, and pilomyxoid astrocytoma, n = 1 each), lipid peaks were small or absent. CONCLUSIONS Large lipid peaks on (1)H-MRS images of tumors without central necrosis were characteristic of malignant lymphomas. Conversely, small or absent lipid peaks in intraaxial tumors without central necrosis were strongly suggestive of glioma.

Multicentric Glioma Develops via a Mutant IDH1-Independent Pathway: Immunohistochemical Study of Multicentric Glioma

Multicentric gliomas are very rare. Due to differences in their tumor types they remain enigmatic. We focused on the pathogenesis of multicentric gliomas and compared their immunoprofile with that of solitary gliomas. This retrospective study included 6 males and 8 females with multicentric glioma (8 glioblastomas, 2 anaplastic astrocytomas, 4 diffuse astrocytomas). Their age ranged from 27 to 75 years and all were treated between 2004 and June 2015. The expression of mutant isocitrate dehydrogenase 1 (IDH1), α-thalassemia X-linked intellectual disability (ATRX), p53, phosphatase and tensin homolog (PTEN), and epidermal growth factor receptor (EGFR) was examined immunohistochemically; for 1p19q analysis we used fluorescence in situ hybridization (FISH). In all patients, immunohistochemical staining was negative for mutant IDH1 and cytoplasmic PTEN; only 1 patient (7.1%) manifested nuclear PTEN positivity. FISH for 1p19q codeletion was negative in all 9 examined samples; 5 of 14 specimens (35.7%) were p53-positive, 9 (64.3%) were EGFR-positive, and 4 (28.6%) were ATRX-negative. The MIB-1 labeling index was 0.9-15.6% for grades II and III, and ranged between 17.3 and 52.4% for glioblastoma. Our results suggest that the pathogenesis of multicentric gliomas is different from the mutant IDH1-R132H pathogenesis of lower-grade glioma and secondary glioblastomas. More studies are needed to confirm the molecular mechanisms underlying the pathogenesis of multicentric glioma.

Evaluation of cerebellar mutism by arterial spin-labeling perfusion magnetic resonance imaging in a patient with atypical teratoid/rhabdoid tumor (AT/RT): a case report

Cerebellar mutism is a well-known complication of posterior fossa surgery. However, the cause of this syndrome and its exact mechanisms are still unknown. According to the literature, some have reported findings of single photon emission tomography (SPECT) in patients with cerebellar mutism [1–3]; however, these findings in individual cases are not conclusive enough to explain the mechanism of mutism. Magnetic resonance (MR) perfusion imaging provides useful information about vascularization. MR perfusion of central nervous system usually has been determined by using dynamic susceptibility weighted contrast material-enhanced MR imaging with echo-planar MR imaging (MRI) sequences. The arterial spin-labeling (ASL) is an alternative MR perfusion imaging technique that has primarily been used to measure cerebral blood flow (CBF) without the use of extrinsic tracers. At least a 3 Tor higher fieldMRmachine is necessary to obtain reliable CBF signals in ASL. TheASL approach is increasingly recognized as a noninvasive method for quantitative CBF measurement in stroke assessment [4, 5], neurodegenerative diseases [6, 7], and brain tumors [8–11]. Moreover, it is especially relevant in the field of pediatrics as the adverse reactioninducing compound gadolinium is unnecessary in this method. This is the first report that shows the clinical benefit of ASL for CBF evaluation in an infant with cerebellar mutism.

Post-traumatic Unilateral Avulsion of the Abducens Nerve with Damage to Cranial Nerves VII and VIII: Case Report

Traumatic injuries of the abducens nerve as a consequence of facial and/or head trauma occur with or without associated cervical or skull base fracture. This is the first report on unilateral avulsion of the abducens nerve in a 29-year-old man with severe right facial trauma. In addition, he exhibited mild left facial palsy, and moderate left hearing disturbance. Magnetic resonance imaging (MRI) using fast imaging employing steady-state acquisition (FIESTA) revealed avulsion of left sixth cranial nerve. We recommend thin-slice MR examination in patients with abducens palsy after severe facial and/or head trauma.

Prognostic implications of the subcellular localization of survivin in glioblastomas treated with radiotherapy plus concomitant and adjuvant temozolomide

OBJECTIVE Currently, the standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Various prognostic biomarkers for GBM have been described, including survivin expression. The aim of this study was to determine whether the subcellular localization of survivin correlates with GBM prognosis in patients who received the standard treatment protocol. METHODS The authors retrospectively examined the subcellular localization of survivin (nuclear, cytoplasmic, or both) using immunohistochemistry in 50 patients with GBM who had received the standard treatment. The relationship between survivin localization and overall survival (OS) was assessed with uni- and multivariate analyses including other clinicopathological factors (age, sex, Karnofsky Performance Scale [KPS] score, extent of resection, the use of second-line bevacizumab, O6-methylguanine-DNA methyltransferase [MGMT] status, and MIB-1 labeling index). RESULTS Log-rank tests revealed that patient age, KPS score, extent of resection, MGMT status, and survivin localization (p < 0.0001) significantly correlated with OS. Multivariate analysis indicated that patient age, MGMT status, and survivin localization significantly correlated with OS. Patients with nuclear localization of survivin had a significantly shorter OS than those in whom survivin expression was exclusively cytoplasmic (median OS 19.5 vs 31.7 months, respectively, HR 5.690, 95% CI 2.068-17.612, p = 0.0006). There was no significant difference in OS between patents whose survivin expression was exclusively nuclear or nuclear/cytoplasmic. CONCLUSIONS Nuclear expression of survivin is a factor for a poor prognosis in GBM patients. Subcellular localization of survivin can help to predict OS in GBM patients treated with the standard protocol.

p16 Gene Transfer Induces Centrosome Amplification and Abnormal Nucleation Associated with Survivin Downregulation in Glioma Cells.

Objective: In human glioma cells, p16 gene transfer induced G1/S arrest, increased radiosensitivity and abnormal nucleation (especially bi- and multinucleation). Survivin suppression caused G2/M arrest, radiosensitization and an increase in aneuploidy accompanied by centrosome amplification. Abnormal nucleation and aneuploidy represent chromosome instability (CIN), and it is well known that centrosome amplification leads to CIN. However, little has been reported that suggests that transferring p16 causes centrosome overduplication during the G1/S phase. Methods: The p16 gene was transferred into p16-null human glioma cell lines (U251MG and D54MG) using adenovirus with or without irradiation. Centrosome amplification was evaluated by immunofluorescence. We also investigated the DNA replication licensing factor CDT1, its inhibitor geminin and survivin expression as regulators of chromosomal segregation. Results: p16 gene transfer with radiation initiated the greatest degree of centrosome overduplication. CDT1 showed low levels, geminin was unchanged and survivin decreased in Ax-hp16-infected cells with radiation. Those changes of factors affecting DNA licensing or chromosomal segregation might contribute to CIN. Conclusion: p16 transfer caused centrosome amplification even in G1/S phase-arrested cells. This suggests that p16 is involved in abnormal nucleation and radiosensitization in human glioma cells.