Pretreatment ADC Histogram Analysis Is a Predictive Imaging Biomarker for Bevacizumab Treatment but Not Chemotherapy in Recurrent Glioblastoma

BACKGROUND AND PURPOSE:Pre-treatment ADC characteristics have been shown to predict response to bevacizumab in recurrent glioblastoma multiforme. However, no studies have examined whether ADC characteristics are specific to this particular treatment. The purpose of the current study was to determine whether ADC histogram analysis is a bevacizumab-specific or treatment-independent biomarker of treatment response in recurrent glioblastoma multiforme.MATERIALS AND METHODS:Eighty-nine bevacizumab-treated and 43 chemotherapy-treated recurrent glioblastoma multiformes never exposed to bevacizumab were included in this study. In all patients, ADC values in contrast-enhancing ROIs from MR imaging examinations performed at the time of recurrence, immediately before commencement of treatment for recurrence, were extracted and the resulting histogram was fitted to a mixed model with a double Gaussian distribution. Mean ADC in the lower Gaussian curve was used as the primary biomarker of interest. The Cox proportional hazards model and log-rank tests were used for survival analysis.RESULTS:Cox multivariate regression analysis accounting for the interaction between bevacizumab- and non-bevacizumab-treated patients suggested that the ability of the lower Gaussian curve to predict survival is dependent on treatment (progression-free survival, P = .045; overall survival, P = .003). Patients with bevacizumab-treated recurrent glioblastoma multiforme with a pretreatment lower Gaussian curve > 1.2 μm²/ms had a significantly longer progression-free survival and overall survival compared with bevacizumab-treated patients with a lower Gaussian curve < 1.2 μm²/ms. No differences in progression-free survival or overall survival were observed in the chemotherapy-treated cohort. Bevacizumab-treated patients with a mean lower Gaussian curve > 1.2 μm²/ms had a significantly longer progression-free survival and overall survival compared with chemotherapy-treated patients.CONCLUSIONS:The mean lower Gaussian curve from ADC histogram analysis is a predictive imaging biomarker for bevacizumab-treated, not chemotherapy-treated, recurrent glioblastoma multiforme. Patients with recurrent glioblastoma multiforme with a mean lower Gaussian curve > 1.2 μm²/ms have a survival advantage when treated with bevacizumab.

Malignant gliomas, including anaplastic astrocytomas, anaplastic oligodendrogliomas, anaplastic mixed oligoastrocytomas, and glioblastoma multiforme (GBM), account for almost 80% of malignant primary brain tumors.¹ GBM, the most aggressive and malignant type of primary brain tumor, has a mean survival of only 12–14 months under the current standard of care of radiotherapy combined with concurrent temozolomide, along with adjuvant temozolomide.^2,3 GBMs are highly vascular tumors, recruiting existing vasculature and generating neovasculature from excessive levels of circulating angiogenic growth factors, including vascular endothelial growth factor (VEGF). The highly vascular nature of these tumors has led to a new class of antiangogenic agents, for which there are many ongoing clinical trials in GBM.^4–6Standard imaging techniques are limited in their ability to evaluate the effectiveness of antiangiogenic therapy in malignant gliomas due to a reduction in contrast enhancement. These limitations have resulted in a surge of more advanced imaging biomarkers aimed at predicting response to therapy, as summarized in various review articles.^7,8 Among these new imaging biomarkers showing promise are diffusion MR imaging techniques,^9–18 including ADC histogram analysis. Previous results have shown that pretreatment ADC histogram analysis performed within the contrast-enhancing tumor regions can stratify patients with recurrent GBM into high- and low-risk groups. When using a double Gaussian mixed model to represent the ADC histogram, previous studies have shown that a lower mean value of the Gaussian curve (ADC_L) results in a significantly shorter progression-free survival (PFS) and overall survival (OS) in both single-institution⁹ and multicenter clinical trial data¹⁹ when evaluating bevacizumab in malignant gliomas. An important question remains as to whether ADC histogram analysis is a predictive biomarker specific to antiangiogenic therapy in recurrent GBM or whether it is a predictive biomarker independent of the particular treatment administered. In the current study, we performed ADC histogram analysis in patients with recurrent GBM from the University of California, Los Angeles (UCLA) treated with bevacizumab and those with recurrent GBM from the University of Toronto treated with a variety of chemotherapies and never exposed to bevacizumab, to determine whether ADC histogram analysis performed before treatment in recurrent GBM is a bevacizumab-specific or treatment-independent biomarker of treatment response.     

Altered functional connectivity of the default mode network in diffuse gliomas measured with pseudo-resting state fMRI

The purpose of the current study was to explore whether brain tumors disrupt the integrity of the default mode network (DMN), a well-characterized resting-state fMRI network. We evaluated whether tumor grade, volume, post-surgical/clinical status, or location decreased the functional connectivity within the DMN in patients with gliomas. Task-based fMRI data was obtained from 68 diffuse glioma patients and 12 healthy volunteers. Pseudo-resting state fMRI data was calculated from task-based fMRI data using standard techniques. Data was preprocessed and DMN integrity was compared across WHO grade, tumor volume surgical status (new vs. recurrent tumors), age, and KPS using univariate and multivariate linear models. WHO grade was the most significant predictor of DMN integrity (P = 0.004), whereas T2 hyperintense lesion volume was not a predictor (P = 0.154). DMN integrity was lower in high-grade (WHO III–IV) compared with low-grade (WHO II) patients (P = 0.020). Tumors in the left parietal lobe showed a more impaired DMN compared with tumors in the frontal lobe, while tumors within and outside the network nodes did not differ significantly. Results suggest higher tumor grade along with prior surgery and/or treatment cause the largest reduction in DMN functional connectivity in patients with primary gliomas, and that tumor location has an impact on connectivity.     

Caudal-posteroanterior view in coronary arteriography

Posteroanterior (PA) and caudally angulated PA views were obtained in 20 patients undergoing routine coronary arteriography. Although the left main coronary artery (LMCA) was seen well on both views in all patients, the PA-caudal view improved depiction of the LMCA bifurcation in 15 (75%). In addition, the PA-caudal view markedly improved depiction of the circumflex artery, affording optimal depiction of this artery and its branches in 78%-89% of patients. Neither the PA nor the PA-caudal view allowed adequate depiction of the left anterior descending artery. Thus, the PA-caudal view should supplant the PA view in routine coronary arteriography.     

Morphological changes due to Lead exposure and the influence of DMSA on the gill tissues of the freshwater fish, Catla catla

Catla catla fingerlings were reared in freshwater and exposed to 15.5 ppm concentration of lead for 60 days. The morphological changes on the gill of the C. catla fingerlings due to lead intoxication and the effect of DMSA (meso 2,3-dimercaptosuccinic acid) on the affected tissues were observed using Scanning Electron Microscope. It has been found that the lead treated gill tissues showed certain marked changes, such as cell hypertrophy, alteration in the lamellar surfaces, epithelial hyperplasia and the fusion of adjacent lamellae. The antidote DMSA treatment reduces the toxic effects and helps the recovery of gill tissue and its return to the level of the control/normal.     

Can an EASYcare based dementia training programme improve diagnostic assessment and management of dementia by general practitioners and primary care nurses? The design of a randomised controlled trial

Background  

Early diagnosis of dementia benefits both patient and caregiver. Nevertheless, dementia in primary care is currently under-diagnosed. Some educational interventions developed to improve dementia diagnosis and management were successful in increasing the number of dementia diagnoses and in changing attitudes and knowledge of health care staff. However, none of these interventions focussed on collaboration between GPs and nurses in dementia care. We developed an EASYcare-based Dementia Training Program (DTP) aimed at stimulating collaboration in dementia primary care. We expect this program to increase the number of cognitive assessments and dementia diagnoses and to improve attitudes and knowledge of GPs and nurses.     

Mesoatrial shunts for Budd-Chiari syndrome and inferior vena cava thrombosis: angiographic and hemodynamic evaluations

When inferior vena caval obstruction complicates the Budd-Chiari syndrome, conventional portosystemic shunts are not possible. The mesoatrial shunt has been devised to enable portal and sinusoidal decompression in these patients. Findings in 12 patients with Budd-Chiari syndrome and inferior vena caval obstruction in whom a mesoatrial shunt was performed are reported. Preoperative inferior vena cavography with pressure measurements is essential to determine the appropriate shunt procedure. Postoperatively, shunt patency is assessed with superior mesenteric arterial portography. Where possible, transvenous catheterization of the shunt is performed to confirm patency and assess hemodynamic function.     

Expert system-controlled image display

Conventional computer-based medical expert systems deliver advice to physicians as written text. While such advice is useful, it has distinct limitations in a visually oriented discipline such as diagnostic radiology, in which decisions often depend on pattern recognition and appreciation of subtle morphologic features. The authors developed a prototype expert computer system, IMAGE/ICON, which displays groups of images sorted into a series of axes based on different ways in which they may be similar. They may share a common feature, group of features, causes, or clinical setting. IMAGE/ICON may display examples of morphologic variations of a dominant finding or a spectrum of abnormalities seen in an specific disease or group of diseases. The system also assembles a written analysis of key features of a case. Such a tool may be useful as a diagnostic aid or for continuing medical education. It is likely to have particular impact in the form of an intelligent radiologic workstation, as picture archiving and communication systems become available.     

Pellegrini-Stieda disease

Pellegrini-Stieda disease is a condition occasionally observed on routine radiographic examinations of the knee. A literature survey revealed little in the way of explanation or therapeutic management of this disorder. An overview of this condition with an emphasis on etiological theory and treatment is offered along with two classic radiographic examples.     

尿酶检测早期诊断庆大霉素肾脏损害的动物实验与临床研究

采用犬庆大霉素肾中毒模型,结合临床病例,检测尿丙氨酸氨基肽酶、N-乙酰—β—氨基葡萄糖苷酶、γ-谷氨酰转肽酶、乳酸脱氢酶的变化和犬肾超微结构改变。结果显示,治疗剂量庆大霉素对肾脏具有损害作用,中毒量的损害明显加重;处于亚临床期肾病变者,庆大霉素显著加重其毒性损害。检测尿酶的变化可以早期反映出这种肾毒性损害,是一种灵敏的早期监测指标。