Infiltrative patterns of glioblastoma: Identification of tumor progress using apparent diffusion coefficient histograms.

PURPOSE: To investigate whether apparent diffusion coefficient (ADC) histogram analysis can differentiate between patients presenting T2-progress and patients presenting stable T2-signal in glioblastoma. MATERIALS AND METHODS: Fourteen patients presenting an isolated T2-progress and a matched control group exhibiting stable disease were included. Relative ADC value distribution within tumoral and peritumoral FLAIR hyperintensities were evaluated using ADC-histogram analysis. Severity and frequency of ADC shift between baseline, T2-progress, and subsequent T1-progress were analyzed using the Wilcoxon test. RESULTS: The shift of ADC histograms either to higher or to lower values in case of T2-progress was significantly more severe than in the control group (P value 0.05). Furthermore, a significant shift toward lower ADC values (P value 0.02) was detected when comparing ADC histograms of patients with T2-progress and subsequent T1-progress. CONCLUSION: The basis for the observed ADC shift in isolated T2-progress may be time dependent: Initially, formation of peritumoral edema may cause an increase of ADC values that is followed by tumor cells infiltrating the surrounding tissue, causing a subsequent decrease of ADC values. The shift toward lower ADC values in case of subsequent T1-progress confirms this hypothesis and provides further evidence for T2-progress being an intermediate step between stable disease (SD) and T1-progress.

Reduced prefrontal and orbitofrontal gray matter in female adolescents with borderline personality disorder: is it disorder specific?

There is evidence that adults with borderline personality disorder (BPD) are characterized by abnormalities in frontolimbic brain areas. In this study we aimed to determine whether brain volume alterations already exist in adolescents with BPD. Sixty female right-handed individuals (age range, 14-18 years), 20 with a DSM-IV diagnosis of borderline personality disorder, 20 patients with a DSM-IV defined current psychiatric disorder and 20 healthy control subjects were included. Groups were matched for age and IQ. Using a 3 T MRI scanner, we collected 1 mm axial sections using a three-dimensional sagittal isotropic Magnetization Prepared Rapid Acquisition Gradient Echo (MPRAGE) sequence. Images were analyzed using voxel-based morphometry (VBM). Voxel-based analysis revealed that adolescents with BPD showed reduced gray matter in the dorsolateral cortex (DLPFC) bilaterally and in the left orbitofrontal cortex (OFC) relative to healthy control subjects. Adolescent clinical control subjects displayed significantly decreased gray matter volume in the right DLPFC in comparison with healthy control subjects. No significant gray matter differences were detected between the BPD group and the clinical control group. No group differences were found in the limbic system or in any white matter structures. The present study indicates that the early morphological changes in BPD are located in the PFC. However, these changes may not be BPD specific since similar changes were found in the clinical control group. Changes in limbic brain volumes and white matter structures might occur over the course of the illness.

Deferasirox in MDS patients with transfusion-caused iron overload--a phase-II study.

Blood transfusions represent a main component of supportive care in myelodysplastic syndromes (MDS). To avoid organ damage caused by transfusion-dependent iron overload, an adequate iron chelation therapy is required. Recently, a new oral iron chelator deferasirox (ICL670, Exjade) has become available. A study was conducted to demonstrate the efficacy and tolerability of deferasirox in transfusion-dependent iron-overloaded patients with MDS. The efficacy of deferasirox was monitored by changes in serum ferritin, bone marrow iron, and liver iron concentration (LIC), as determined by T2*-weighted magnetic resonance imaging. Twelve patients with MDS of different subtypes (median age 76 years, range 53-91) were enrolled. Deferasirox administered in a once-daily dose of 20-30 mg/kg for 12 months was effective in reducing median ferritin concentration from 1,515 microg/L (range 665-6,900) to 413 microg/L (range 105-3,052). Within the first 4 weeks of treatment before the continuous decline of ferritin levels, the values markedly rose in eight of 12 patients. The median LIC declined from 315 to 230 micromol/g (p=0.02) at the end of study, accompanied by a reduction of bone marrow siderosis. The most common adverse events were mild and transient gastrointestinal disturbances, skin rash, nonprogressive transient increases in serum creatinine and urine beta2-microglobulin, and a temporary reduction of the creatinine clearance. The renal parameters normalized after end of treatment. No hematologic toxicities were observed. Deferasirox proved to be effective in transfusion-dependent iron overload in MDS by mobilizing iron deposits in liver and at least stabilizing iron stores in bone marrow.

Disorder-specific white matter alterations in adolescent borderline personality disorder.

BACKGROUND: The pathogenesis of borderline personality disorder (BPD) is complex and not fully understood. Using diffusion tensor imaging, recent studies suggest that white matter abnormalities may occur in adult patients with BPD. However, deeper insight into the disorder-specific developmental psychobiology (e.g., analysis of adolescents with BPD; inclusion of clinical control groups) is missing. METHODS: Twenty adolescent patients with BPD (aged 14-18 years), 20 healthy, and 20 clinical control subjects were assessed using diffusion tensor imaging. All subjects were right-handed girls, matched for age and IQ. Microstructural parameters were analyzed via tractography of the main bundles in the limbic system and using Tract-Based Spatial Statistics, an explorative, global approach. RESULTS: BPD was associated with decreased fractional anisotropy in the fornix when compared with clinical (p < .001) or healthy (nonsignificant trend) control subjects. Using Tract-Based Spatial Statistics, significant disorder-specific white matter alterations were found in the long association bundles interconnecting the heteromodal association cortex and in connections between the thalamus and hippocampus. CONCLUSIONS: The study strongly supports the hypothesis that white matter alterations play a key role in the pathogenesis of BPD. These disorder-specific alterations include white matter pathways involved in emotion regulation but also affect parts of the heteromodal association cortex that are related to emotion recognition. Our findings unify previously documented deficits in emotion recognition and regulation and suggest that a large-scale network of emotion processing is disrupted in BPD. Continued research is essential to evaluate the predictive value of these early disruptions in a clinical context.

Hemosiderin deposition in the brain as footprint of high-altitude cerebral edema.

OBJECTIVE: Based on recent findings of microhemorrhages (MHs) in the corpus callosum (CC) in 3 individuals after nonfatal high-altitude cerebral edema (HACE), we hypothesized that hemosiderin depositions in the brain after high-altitude exposure are specific for HACE and remain detectable over many years. METHODS: This was a cross-sectional study involving 37 mountaineers in 4 groups: 10 had experienced HACE, 8 high-altitude pulmonary edema, 11 severe acute mountain sickness, and 8 had climbed to altitudes ≥6,962 m without developing any high-altitude illness. HACE was defined as ataxia necessitating assistance with walking and/or decreased consciousness. Within <1 to 38 months after the qualifying incident, MRI of the brain was performed using a 3-tesla scanner and high-resolution susceptibility-weighted magnetic resonance sequences for detection of hemosiderin depositions, which were quantified by a score. RESULTS: Unequivocal MHs located in the splenium of the CC were found in 8 subjects and questionable MHs were found in 2 subjects 1 to 35 months after HACE. They were located outside the CC in 5 more severe cases. MHs remained unchanged in those reexamined after 12 to 50 months. A few unequivocal MHs in the splenium of the CC were found in one subject after severe acute mountain sickness, while one subject with high-altitude pulmonary edema and 2 of the extreme altitude climbers had questionable lesions. In all other subjects, MHs were unequivocally absent. CONCLUSIONS: MHs detectable by susceptibility-weighted MRI predominantly in the splenium of the CC are long-lasting footprints of HACE.

Differentiation of glioblastoma and primary CNS lymphomas using susceptibility weighted imaging.

INTRODUCTION: Reliable differentiation between glioblastoma and primary CNS lymphoma (PCNSL) using conventional MR imaging is challenging, since both entities may show similar appearance on structural MR imaging. Here we analyzed if the appearance of intratumoural susceptibility signals (ITSS) on susceptibility weighted imaging (SWI) may differentiate between both entities. METHODS AND MATERIALS: SWI and contrast enhanced T1-weighted images were acquired from 15 patients with newly diagnosed PCNSL (14 B-cell PCNSL, 1 T-cell PCNSL) and 117 patients with newly diagnosed glioblastoma with a 3 Tesla MR. Additional phase images were available in 8 patients with PCNSL and 88 patients with glioblastoma. Appearance of ITSS was assessed by two readers on SWI and the size of the enhancing lesions on contrast enhanced T1-weighted images were measured. Furthermore it was assessed if ITSS displayed more clearly on SWI or on phase images. RESULTS: ITSS were detected in 106 (reader 1) and 109 (reader 2) glioblastoma, respectively. Both readers identified ITSS within the T-cell PCNSL while both readers did not identify any ITSS within the 14 Bcell PCNSL. Interrarter variability as determined by Cohen κ was excellent for glioblastoma (κ=0.938) and for PCNSL (κ=1). The medium size of the enhancing lesion of the glioblastoma that did not harbour ITSS was significantly smaller than the size of the glioblastoma exhibiting ITSS (p<0.008). All identified ITSS displayed more clearly on SWI than on phase images. CONCLUSION: Presence of ITSS differentiates reliably between glioblastoma and B-cell PCNSL and provides a fast bases for the clinical decision without causing any postprocessing work.

Relevance of T2 signal changes in the assessment of progression of glioblastoma according to the Response Assessment in Neurooncology criteria.

BACKGROUND: According to the Response Assessment in Neurooncology (RANO) criteria, significant nonenhancing signal increase in T2-weighted images qualifies for progression in high-grade glioma (T2-progress), even if there is no change in the contrast-enhancing tumor portion. The purpose of this retrospective study was to assess the frequency of isolated T2-progress and its predictive value on subsequent T1-progress, as determined by a T2 signal increase of 15% or 25%, respectively. The frequency of T2-progress was correlated with antiangiogenic therapy. PATIENTS AND METHODS: MRI follow-up examinations (n = 777) of 144 patients with histologically proven glioblastoma were assessed for contrast-enhanced T1 and T2-weighted images. Examinations were classified as T1-progress, T2-progress with 15% or 25% T2-signal increase, stable disease, or partial or complete response. RESULTS: Thirty-five examinations revealed exclusive T2-progress using the 15% criterion, and only 2 examinations qualified for the 25% criterion; 61.8% of the scans presenting T2-progress and 31.5% of the scans presenting stable disease revealed T1-progress in the next follow-up examination. The χ(2) test showed a highly significant correlation (P < .001) between T2-progress, with the 15% criterion and subsequent T1-progress. No correlation between antiangiogenic therapy and T2-progress was shown. CONCLUSION: Tumor progression, as determined by both contrast-enhanced T1 and T2 sequences is more frequently diagnosed than when considering only contrast-enhanced T1 sequences. Definition of T2-progress by a 15% T2-signal increase criterion is superior to a 25% criterion. The missing correlation of T2-progress and antiangiogenic therapy supports the hypothesis of T2-progress as part of the natural course of the tumor disease.