Can Apparent Diffusion Coefficient (ADC) maps replace Diffusion Tensor Imaging (DTI) maps to predict the volumetric response of meningiomas to Gamma Knife Radiosurgery?

PURPOSE: Noninvasive methods are desired to predict the treatment response to Stereotactic Radiosurgery (SRS) to improve individual tumor management. In a previous study, we demonstrated that Diffusion Tensor Imaging (DTI)-derived parameter maps significantly correlate to SRS response. This study aimed to analyze and compare the predictive value of intratumoral ADC and DTI parameters in patients with meningiomas undergoing radiosurgery. METHODS: MR images of 70 patients treated with Gamma Knife SRS for WHO grade I meningiomas were retrospectively reviewed. MR acquisition included pre- and post-treatment DWI and DTI sequences, and subtractions were calculated to assess for radiation-induced changes in the parameter values. RESULTS: After a mean follow-up period (FUP) of 52.7 months, 69 of 70 meningiomas were controlled, with a mean volume reduction of 34.9%. Whereas fractional anisotropy (FA) values of the initial exam showed the highest correlation to tumor volume change at the last FU (CC = - 0.607), followed by the differences between first and second FU values of FA (CC = - 0.404) and the first longitudinal diffusivity (LD) value (CC = - 0.375), the correlation coefficients of all ADC values were comparably low. Nevertheless, all these correlations, except for ADC measured at the first follow-up, reached significance. CONCLUSION: For the first time, the prognostic value of ADC maps measured in meningiomas before and at first follow-up after Gamma Knife SRS, was compared to simultaneously acquired DTI parameter maps. Quantities assessed from ADC maps present significant correlations to the volumetric meningioma response but are less effective than correlations with DTI parameters.

MRI radiomics in the prediction of the volumetric response in meningiomas after gamma knife radiosurgery.

PURPOSE: This report presents the first investigation of the radiomics value in predicting the meningioma volumetric response to gamma knife radiosurgery (GKRS). METHODS: The retrospective study included 93 meningioma patients imaged by three Tesla MRI. Tumor morphology was quantified by calculating 337 shape, first- and second-order radiomic features from MRI obtained before GKRS. Analysis was performed on original 3D MR images and after their laplacian of gaussian (LoG), logarithm and exponential filtering. The prediction performance was evaluated by Pearson correlation, linear regression and ROC analysis, with meningioma volume change per month as the outcome. RESULTS: Sixty calculated features significantly correlated with the outcome. The feature selection based on LASSO and multivariate regression started from all available 337 radiomic and 12 non-radiomic features. It selected LoG-sigma-1-0-mm-3D_firstorder_InterquartileRange and logarithm_ngtdm_Busyness as the predictively most robust and non-redundant features. The radiomic score based on these two features produced an AUC = 0.81. Adding the non-radiomic karnofsky performance status (KPS) to the score has increased the AUC to 0.88. Low values of the radiomic score defined a homogeneous subgroup of 50 patients with consistent absence (0%) of tumor progression. CONCLUSION: This is the first report of a strong association between MRI radiomic features and volumetric meningioma response to radiosurgery. The clinical importance of the early and reliable prediction of meningioma responsiveness to radiosurgery is based on its potential to aid individualized therapy decision making.

FMNL2 regulates gliovascular interactions and is associated with vascular risk factors and cerebrovascular pathology in Alzheimer's disease.

Alzheimer's disease (AD) has been associated with cardiovascular and cerebrovascular risk factors (CVRFs) during middle age and later and is frequently accompanied by cerebrovascular pathology at death. An interaction between CVRFs and genetic variants might explain the pathogenesis. Genome-wide, gene by CVRF interaction analyses for AD, in 6568 patients and 8101 controls identified FMNL2 (p = 6.6 × 10-7). A significant increase in FMNL2 expression was observed in the brains of patients with brain infarcts and AD pathology and was associated with amyloid and phosphorylated tau deposition. FMNL2 was also prominent in astroglia in AD among those with cerebrovascular pathology. Amyloid toxicity in zebrafish increased fmnl2a expression in astroglia with detachment of astroglial end feet from blood vessels. Knockdown of fmnl2a prevented gliovascular remodeling, reduced microglial activity and enhanced amyloidosis. APP/PS1dE9 AD mice also displayed increased Fmnl2 expression and reduced the gliovascular contacts independent of the gliotic response. Based on this work, we propose that FMNL2 regulates pathology-dependent plasticity of the blood-brain-barrier by controlling gliovascular interactions and stimulating the clearance of extracellular aggregates. Therefore, in AD cerebrovascular risk factors promote cerebrovascular pathology which in turn, interacts with FMNL2 altering the normal astroglial-vascular mechanisms underlying the clearance of amyloid and tau increasing their deposition in brain.

Texture Analysis of Standard Magnetic Resonance Images to Predict Response to Gamma Knife Radiosurgery in Vestibular Schwannomas.

PURPOSE: To search for texture features of routine magnetic resonance imaging to predict tumor volume reduction and transient versus permanent tumor progression of vestibular schwannomas treated by Gamma Knife stereotactic radiosurgery. MATERIALS AND METHODS: Included were 23 patients with vestibular schwannomas treated in our center and followed over a period of 23.7-80.3 months (mean 42.7). Magnetic resonance imaging was performed on a 3-Tesla scanner and included T1-weighted images with and without contrast enhancement, T2-weighted, and fluid-attenuated inversion recovery images. Volumetric results were followed longitudinally over time and correlated to texture features as mean, minimum, maximum, standard deviation, skewness, and kurtosis of normalized signals taken from regions of interest covering the total tumor volume. RESULTS: In total, 14 tumors showed early progression during the first 5-18 months (2 cases permanent, 12 cases transient), whereas 9 tumors regressed immediately after SRS. Kurtosis of T2-weighted image intensity values turned out to predict progression best with a sensitivity and specificity of 71% and 78%. From all texture feature parameters, only the minimum of the normalized T2-weighted image intensity values correlated significantly to the final reduction of tumor volume per month (correlation coefficient = -0.634, P < 0.05, corrected for false discovery rate). CONCLUSIONS: Texture feature analysis helps to predict permanent versus transient enlargement and final volume reduction of schwannomas after SRS. Thus, alternative treatment strategies might be considered, mainly in large tumors, where further clinical deterioration cannot be excluded. To confirm these results, a prospective study including more cases and a longer follow-up period is necessary.

Compression of the middle cerebellar tract by posterior fossa tumors before and after Gamma Knife radiosurgery studied with diffusion tensor imaging.

PURPOSE: To investigate if clinically asymptomatic compression of the middle cerebellar tract by extracerebral posterior fossa tumors can produce changes in diffusion tensor imaging (DTI) parameters and if these changes return to normal after Gamma Knife radiosurgery (GKRS). MATERIAL AND METHODS: In 22 patients (12 female, mean age 53.8 years) with posterior fossa tumors (14 schwannomas and 8 meningiomas), the middle cerebellar tract was tracked using DTI data. DTI parameters, such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) within these tracts were determined separately on the tumor side and on the contra-lateral side. As a surrogate parameter of tract compression, we used the distance between a tangential line extending between the anterior, not affected part of the pons and the cerebellum, and the furthest extension of the tumor into the lateral rim of the pons. In a subgroup of 15 patients, DTI parameters were recorded after a follow-up of more than 2 years (mean follow-up time 37.5 months) after GKRS and compared to initial findings. RESULTS: Before GKRS, all DTI parameters within the compressed tract had increased. The increase in MD correlated significantly with the degree of tract compression (c = 0.443, p < 0.05). Follow-up examinations after GKRS showed reduction in FA and AD, whereas MD and RD increased. After correction for time elapsed after treatment and tumor type, the changes of MD and AD following treatment correlated significantly with the reduction of tract compression, but not with radiation dose. CONCLUSION: Although without obvious clinical symptoms, disorders of the middle cerebellar tract, as in the case of posterior fossa tumors, persist after reduction of tumor size. Because of the significant correlation between the change of parameters and the reduction of tract compression, initial compression and consequent relief are regarded as the main factors responsible for persistent disorders of the middle cerebellar tract. Radiosurgery dose did not contribute significantly to changes in DTI parameters.

Adaptation of visual cortex to damage of visual pathways in suprasellar tumors before and after gamma knife radiosurgery.

PURPOSE: To demonstrate that lesions of the visual pathways due to suprasellar tumors are accompanied by alterations of the visual cortex and to see if these alterations are reversible after treatment of tumors by gamma knife radiosurgery. MATERIALS AND METHODS: In 36 patients with peri-optic tumors and defects of their visual fields and in an age-matched control group, magnetic resonance imaging was performed before and after treatment. T1 weighted images were evaluated by voxel-based morphometry and correlated to the degree of visual field defects. RESULTS: In patients, grey matter density and cortical thickness were reduced in all parts of the occipital cortex, reaching significance (p < 0.05) in the left superior and middle occipital gyri, with correlation to visual field defects. Follow-up scans showed further reduction in all occipital areas. CONCLUSION: As in other peripheral lesions of the optic system, damage of the optic pathways affects the visual cortex. A prospective follow-up study is needed to determine if these alterations are reversible after successful tumor treatment.

Pretreatment texture analysis of routine MR images and shape analysis of the diffusion tensor for prediction of volumetric response after radiosurgery for meningioma.

OBJECTIVEThe goal of this study was to identify parameters from routine T1- and T2-weighted MR sequences and diffusion tensor imaging (DTI) that best predict the volumetric changes in a meningioma after treatment with Gamma Knife radiosurgery (GKRS).METHODSIn 32 patients with meningioma, routine MRI and DTI data were measured before GKRS. A total of 78 parameters derived from first-level texture analysis of the pretreatment MR images, including calculation of the mean, SD, 2.5th and 97.5th percentiles, and kurtosis and skewness of data in histograms on a voxel-wise basis, were correlated with lesion volume change after a mean follow-up period of 3 years (range 19.5-63.3 months).RESULTSSeveral DTI-derived parameters correlated significantly with a meningioma volume change. The parameter that best predicted the results of GKRS was the 2.5th percentile value of the smallest eigenvalue (L3) of the diffusion tensor (correlation coefficient 0.739, p ≤ 0.001), whereas among the non-DTI parameters, only the SD of T2-weighted images correlated significantly with a tumor volume change (correlation coefficient 0.505, p ≤ 0.05, after correction for family-wise errors using false-detection-rate correction).CONCLUSIONSDTI-derived data had a higher correlation to shrinkage of meningioma volume after GKRS than data from T1- and T2-weighted image sequences. However, if only routine MR images are available, the SD of T2-weighted images can be used to predict control or possible progression of a meningioma after GKRS.

Inversion recovery sequences improve delineation of optic pathways in the proximity of suprasellar lesions.

INTRODUCTION: In Gamma Knife Radiosurgery (GKRS) of suprasellar lesions, the exact localization of the visual pathways is important to avoid radiation induced optic neuropathy (RION). Reliable identification of the optic nerve, chiasm and tracts can be challenging using routine magnetic resonance imaging, especially in patients with lesions compressing the optic structures or in patients who had prior operation of suprasellar tumors. This study investigates the application of inversion recovery sequences (Fast gray and white matter acquisition T1 inversion recovery, FGATIR) to improve identification of the optic pathway. METHODS: Inversion recovery sequences were performed on 5 healthy volunteers, varying their inversion times between 400 and 500 ms, and between 800 and 1100 ms. Inversion times were optimized to either suppress or to preserve the signal of the optic structures, while increasing or suppressing the signal of processes within the surrounding cisterns. Inversion recovery sequences were performed before radiosurgery on 10 patients with suprasellar tumors that were compressing or displacing the optic structures. Signal intensities of gray and white matter, of CSF and tumors were measured and subtraction images were calculated. RESULTS: Compared to a standard T1-weighted sequence, delineation of the visual pathways was superior on inversion recovery images, both on images with suppression of the optic structures as well on images with suppression of its surrounding tissues, and was rated best on subtraction images. CONCLUSION: For radiosurgery of suprasellar tumors, inversion recovery sequences can be of valuable benefit for accurate delineation of optic pathway and radiosurgical dose planning in order to avoid radiation-induced normal tissue effects.

"Spontaneous" CSF Fistula due to Transtegmental Brain Herniation in Combination with Signs of Increased Intracranial Pressure and Petrous Bone Hyperpneumatization: An Illustrative Case Report.

Background and Importance Transtegmental brain herniation into the petrous bone is a rare cause of rhinoliquorrhea. Our case presents a combination of several typical clinical and imaging findings illustrating the ongoing etiologic discussion of such cerebrospinal fluid (CSF) fistulas. Clinical Presentation A 53-year-old man presented with nasal discharge after a strong effort to suppress coughing. Imaging revealed a transtegmental herniation of parts of the inferior temporal gyrus into the petrous bone and in addition a combination of signs of chronically increased intracranial pressure and a hyperpneumatization of the petrous bone. The fistula was closed by a middle cranial fossa approach. Conclusion The case illustrates the two main predisposing factors for development of petrous bone CSF fistulas: increased intracranial pressure and thinning of the tegmental roof due to extensive development of air cells. Because the CSF leakage repair does not change the underlying cause, patients have to be informed about the possibility of developing increased intracranial pressure and recurrences of brain herniations at other sites.

Long-term follow-up in two cases of intracranial Rosai-Dorfman Disease complicated by incomplete resection and recurrence.

BACKGROUND: Although intracranial Rosai-Dorfman disease is a principally benign lymphohistiocytosis, some patients run a relapsing or progressive course. However, reports about long-term follow-up are extremely rare. CASE DESCRIPTION: In two patients, initial tumor resection was incomplete or followed by recurrences over 3 years, which finally subsided after application of chemotherapy, and patients remained tumor-free for more than 7 years thereafter. CONCLUSION: Up to now there is no agreement on how to treat complicated cases of intracranial Rosai-Dorfman disease; our good experience with adjuvant chemotherapy and long-term follow-up will contribute to treatment planning in complicated cases.