NDRG1 prognosticates the natural course of disease in WHO grade II glioma.

There is a lack of relevant prognostic and predictive factors in neurooncology besides mutation of isocitrate dehydrogenase 1, codeletion of 1p/19q and promoter hypermethylation of O (6) -methylguanine-DNA-methyltransferase. More importantly, there is limited translation of these factors into clinical practice. The cancer genome atlas data and also clinical correlative analyses suggest a pivotal role for the epidermal growth factor receptor /protein kinase B/mammalian target of rapamycin (mTOR) pathway in both biology and the clinical course of gliomas. However, attempts to stratify gliomas by activating alterations in this pathway have failed thus far. The tumors of 40 patients with WHO grade II gliomas without immediate postoperative genotoxic treatment and known progression and survival status at a median follow-up of 12.2 years were analyzed for expression of the mTOR complex 2 downstream target N-myc downstream regulated gene (NDRG)1 using immunohistochemistry. Baseline characteristics for NDRG1 absent/low versus moderate/high patients were similar. Time to reintervention was significantly longer in the NDRG1 group (P = 0.026). NDRG1 may become a novel biomarker to guide the decision which WHO°II glioma patients may be followed without postsurgical intervention and which patients should receive genotoxic treatment early on. Validation of this hypothesis will be possible with the observational arm of the RTOG 9802 and the pretreatment step of the EORTC 22033/26032 trials.

Measurement of cerebral blood flow volume by extracranial sonography.

Measurement of global cerebral blood flow (CBF) using extracranial duplex sonography has been described, but normal values are still lacking. In 85 healthy adults (median age 43.4 years, range 20 to 80 years), CBF was determined by duplex sonographic examination of both internal carotid arteries and vertebral arteries. The mean global CBF was 630+/-97 mL/min. Global CBF declined with age; sex did not influence the total CBF. When measurements were repeated, the intraindividual variability was low. This noninvasive sonographic measurement of CBF is reproducible, and values correspond closely to those obtained with positron emission tomography and magnetic resonance imaging.

Transcranial sonography of the brain parenchyma: comparison of B-mode imaging and tissue harmonic imaging.

Transcranial color-coded Duplex sonography (TCCS) has been used for the identification of cerebrovascular disorders. Recently, its value in the diagnosis of disorders of the brain parenchyma has been proposed. The object of this study was to determine systematically the echo pattern of the brain parenchyma and to compare conventional B-mode imaging with tissue harmonic imaging (THI). Transcranial sonography (TCS) was performed in 54 healthy individuals through the temporal bone window using conventional B-mode imaging and THI by two experienced investigators. Identification rates for several brain structures were assessed, and the quality of depiction of each method was graded semiquantitatively. In addition, several parts of the ventricular system and the basal cerebral cisterns were measured. Four subjects did not have an adequate bone window for transcranial examination. In the remaining people, the bone window was assessed to be adequate (59%) or excellent (33%). In the majority (> 80%), TCS allowed an unequivocal identification of various brain structures. Inter-rater variability of the assessments of tissue echogenicity and measurements of the ventricular width were found to be low for several structures (e.g., brainstem, thalamus, or 3rd ventricle). The echo pattern of brain tissue in THI is identical to that described for B-mode imaging. Using THI, contours of brain structures were typically visualized more clearly and the reproducibility of measurements was more consistent. In our experience, insonation of the contralateral lobes was limited when depths were higher than 12 cm using THI. In conclusion, TCS allowed the sonographic examination of the brain parenchyma in the majority of our subjects. THI substantially improves the identification of parenchymal structures when the depth is below 12 cm.

Diagnostic impact of cerebral transit time in the identification of microangiopathy in dementia: A transcranial ultrasound study.

BACKGROUND AND PURPOSE: The diagnosis and quantification of microangiopathy in dementia is difficult. The assessment of small-vessel disease requires expensive and sophisticated nuclear medicine techniques. This study was performed to identify microangiopathy related to the integrity of cerebral microcirculation by sonographic measurements (arteriovenous cerebral transit time [cTT]). METHODS: We performed transcranial color-coded duplex sonography in 40 patients with vascular dementia, 20 patients with Alzheimer's disease or Lewy body disease, and 25 age-matched controls. The clinical diagnosis was established by history of dementia and neuroimaging findings. Cognitive impairment was assessed by the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale. cTT is defined as the time required by an ultrasound contrast agent to pass from a cerebral artery to a vein. This was measured by recording the power-Doppler intensity curves in the P2 segment of the posterior cerebral artery and the vein of Galen. Previous studies have shown a prolongation of cTT in patients with cerebral microangiopathy. RESULTS: cTT was substantially prolonged in patients with vascular dementia (5.8 seconds; 25th percentile 4.5; 75th percentile 7.5; U test, P<0.001) compared with controls (3.1 seconds; 2.3; 3.4) but not in patients with degenerative dementia (3.7 seconds; 3.7; 4.2). In patients with vascular dementia, cTT was significantly correlated with cognitive impairment. CONCLUSIONS: cTT may be useful tool to disclose small-vessel disease in demented patients. Examination is noninvasive and quickly performed. It may be also useful in follow-up examinations in patients undergoing therapy.