Comparison of compressed sensing diffusion spectrum imaging and diffusion tensor imaging in patients with intracranial masses.

PURPOSE: To compare compressed diffusion spectrum imaging (CS-DSI) with diffusion tensor imaging (DTI) in patients with intracranial masses. We hypothesized that CS-DSI would provide superior visualization of the motor and language tracts. MATERIALS AND METHODS: We retrospectively analyzed 25 consecutive patients with intracranial masses who underwent DTI and CS-DSI for preoperative planning. Directionally-encoded anisotropy maps, and streamline hand corticospinal motor tracts and arcuate fasciculus language tracts were graded according to a 3-point scale. Tract counts, anisotropy, and lengths were also calculated. Comparisons were made using exact marginal homogeneity, McNemar's and Wilcoxon signed-rank tests. RESULTS: Readers preferred the CS-DSI over DTI anisotropy maps in 92% of the cases, and the CS-DSI over DTI tracts in 84%. The motor tracts were graded as excellent in 80% of cases for CS-DSI versus 52% for DTI; 58% of the motor tracts graded as acceptable in DTI were graded as excellent in CS-DSI (p=0.02). The language tracts were graded as excellent in 68% for CS-DSI versus none for DTI; 78% of the language tracts graded as acceptable by DTI were graded as excellent by CS-DSI (p<0.001). CS-DSI demonstrated smaller normalized mean differences than DTI for motor tract counts, anisotropy and language tract counts (p≤0.01). CONCLUSION: CS-DSI was preferred over DTI for the evaluation of motor and language white matter tracts in patients with intracranial masses. Results suggest that CS-DSI may be more useful than DTI for preoperative planning purposes.

A prospective trial of dynamic contrast-enhanced MRI perfusion and fluorine-18 FDG PET-CT in differentiating brain tumor progression from radiation injury after cranial irradiation.

BACKGROUND: The aim of this study was to assess the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) PET-CT and dynamic contrast-enhanced (DCE) MRI in differentiating tumor progression and radiation injury in patients with indeterminate enhancing lesions after radiation therapy (RT) for brain malignancies. METHODS: Patients with indeterminate enhancing brain lesions on conventional MRI after RT underwent brain DCE-MRI and PET-CT in a prospective trial. Informed consent was obtained. Lesion outcomes were determined by histopathology and/or clinical and imaging follow-up. Metrics obtained included plasma volume (Vp) and volume transfer coefficient (K(trans)) from DCE-MRI, and maximum standardized uptake value (SUVmax) from PET-CT; lesion-to-normal brain ratios of all metrics were calculated. The Wilcoxon rank sum test and receiver operating characteristic analysis were performed. RESULTS: The study included 53 patients (29 treated for 29 gliomas and 24 treated for 26 brain metastases). Progression was determined in 38/55 (69%) indeterminate lesions and radiation injury in 17 (31%). Vpratio (VP lesion/VP normal brain, P < .001), K(trans) ratio (P = .002), and SUVratio (P = .002) correlated significantly with diagnosis of progression versus radiation injury. Progressing lesions exhibited higher values of all 3 metrics compared with radiation injury. Vpratio had the highest accuracy in determining progression (area under the curve = 0.87), with 92% sensitivity and 77% specificity using the optimal, retrospectively determined threshold of 2.1. When Vpratio was combined with K(trans) ratio (optimal threshold 3.6), accuracy increased to 94%. CONCLUSIONS: Vpratio was the most effective metric for distinguishing progression from radiation injury. Adding K(trans) ratio to Vpratio further improved accuracy. DCE-MRI is an effective imaging technique for evaluating nonspecific enhancing intracranial lesions after RT.

Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma.

BACKGROUND: The majority of WHO grades II and III gliomas harbor a missense mutation in the metabolic gene isocitrate dehydrogenase (IDH) and accumulate the metabolite R-2-hydroxyglutarate (R-2HG). Prior studies showed that this metabolite can be detected in vivo using proton magnetic-resonance spectroscopy (MRS), but the sensitivity of this methodology and its clinical implications are unknown. METHODS: We developed an MR imaging protocol to integrate 2HG-MRS into routine clinical glioma imaging and examined its performance in 89 consecutive glioma patients. RESULTS: Detection of 2-hydroxyglutarate (2HG) in IDH-mutant gliomas was closely linked to tumor volume, with sensitivity ranging from 8% for small tumors (<3.4 mL) to 91% for larger tumors (>8 mL). In patients undergoing 2HG-MRS prior to surgery, tumor levels of 2HG corresponded with tumor cellularity but not with tumor grade or mitotic index. Cytoreductive therapy resulted in a gradual decrease in 2HG levels with kinetics that closely mirrored changes in tumor volume. CONCLUSIONS: Our study demonstrates that 2HG-MRS can be linked with routine MR imaging to provide quantitative measurements of 2HG in glioma and may be useful as an imaging biomarker to monitor the abundance of IDH-mutant tumor cells noninvasively during glioma therapy and disease monitoring.

Dynamic Contrast-Enhanced MRI in Low-Grade Versus Anaplastic Oligodendrogliomas.

BACKGROUND AND PURPOSE: Low-grade and anaplastic oligodendrogliomas are often difficult to differentiate on the basis of conventional MR imaging characteristics. Dynamic contrast-enhanced (DCE) MRI can assess tumor microvasculature and has demonstrated utility for predicting glioma grade and prognosis in primary brain tumors. The aim of our study was to evaluate the performance of plasma volume (Vp) and volume transfer coefficient (K(trans) ) derived from DCE MRI in differentiating between grade II and grade III oligodendrogliomas. MATERIALS AND METHODS: Twenty-four consecutive patients with pathologically confirmed oligodendroglioma (World Health Organization grade II, n = 14 and grade III, n = 10) were retrospectively assessed. Pretreatment DCE MRI was performed and regions of interest were manually drawn around the entire tumor volume to calculate Vp and K(trans) . The Mann-Whitney U test and receiver operating characteristic (ROC) analysis were performed to compare pharmacokinetic parameters between the 2 groups. RESULTS: The Vpmean values for grade III oligodendrogliomas were significantly higher (P = .03) than those for grade II oligodendrogliomas. The K(trans) mean values were higher in grade III lesions, but the difference between the 2 groups was not statistically significant (P > .05). Based on ROC analysis, the Vpmean (area under curve = .757, SD = .1) cut-off value that provided the best combination of high sensitivity and specificity to distinguish between grade II and III oligodendrogliomas was 2.35 (P < .03). CONCLUSION: The results of our study suggest the DCE MRI parameter Vpmean can noninvasively differentiate between grade II and grade III oligodendrogliomas.

Dexamethasone stimulated gene expression in peripheral blood is a sensitive marker for glucocorticoid receptor resistance in depressed patients.

Although gene expression profiles in peripheral blood in major depression are not likely to identify genes directly involved in the pathomechanism of affective disorders, they may serve as biomarkers for this disorder. As previous studies using baseline gene expression profiles have provided mixed results, our approach was to use an in vivo dexamethasone challenge test and to compare glucocorticoid receptor (GR)-mediated changes in gene expression between depressed patients and healthy controls. Whole genome gene expression data (baseline and following GR-stimulation with 1.5 mg dexamethasone p.o.) from two independent cohorts were analyzed to identify gene expression pattern that would predict case and control status using a training (N=18 cases/18 controls) and a test cohort (N=11/13). Dexamethasone led to reproducible regulation of 2670 genes in controls and 1151 transcripts in cases. Several genes, including FKBP5 and DUSP1, previously associated with the pathophysiology of major depression, were found to be reliable markers of GR-activation. Using random forest analyses for classification, GR-stimulated gene expression outperformed baseline gene expression as a classifier for case and control status with a correct classification of 79.1 vs 41.6% in the test cohort. GR-stimulated gene expression performed best in dexamethasone non-suppressor patients (88.7% correctly classified with 100% sensitivity), but also correctly classified 77.3% of the suppressor patients (76.7% sensitivity), when using a refined set of 19 genes. Our study suggests that in vivo stimulated gene expression in peripheral blood cells could be a promising molecular marker of altered GR-functioning, an important component of the underlying pathology, in patients suffering from depressive episodes.

Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: evidence from endocrine and gene expression studies.

CONTEXT: Polymorphisms in the gene encoding the glucocorticoid receptor (GR) regulating co-chaperone FKBP5 have been shown to alter GR sensitivity and are associated with an increased risk to develop posttraumatic stress disorder (PTSD). OBJECTIVE: To investigate interactions of the FKBP5 single-nucleotide polymorphism rs9296158 and PTSD symptoms on baseline cortisol level, low-dose dexamethasone suppression, and whole-blood gene expression. DESIGN: Association of FKBP5 genotypes and PTSD symptoms with endocrine measures and genome-wide expression profiles. SETTING: Waiting rooms of general medical and gynecological clinics of an urban hospital at Emory University. PARTICIPANTS: The 211 participants were primarily African American (90.05%) and of low socioeconomic status and had high rates of trauma and PTSD. MAIN OUTCOME MEASURES: Baseline and post-dexamethasone suppression cortisol measures and gene expression levels. RESULTS: In our endocrine study, we found that only risk allele A carriers of rs9296158 showed GR supersensitivity with PTSD; in contrast, baseline cortisol levels were decreased in PTSD only in patients with the GG genotype. Expression of 183 transcripts was significantly correlated with PTSD symptoms after multiple testing corrections. When adding FKBP5 genotype and its interaction with PTSD symptoms, expression levels of an additional 32 genes were significantly regulated by the interaction term. Within these 32 genes, previously reported PTSD candidates were identified, including FKBP5 and the IL18 and STAT pathways. Significant overrepresentation of steroid hormone transcription factor binding sites within these 32 transcripts was observed, highlighting the fact that the earlier-described genotype and PTSD-dependent differences in GR sensitivity could drive the observed gene expression pattern. Results were validated by reverse transcriptase-polymerase chain reaction and replicated in an independent sample (N = 98). CONCLUSIONS: These data suggest that the inheritance of GR sensitivity-moderating FKBP5 polymorphisms can determine specific types of hypothalamic-pituitary-adrenal axis dysfunction within PTSD, which are also reflected in gene-expression changes of a subset of GR-responsive genes. Thus, these findings indicate that functional variants in FKBP5 are associated with biologically distinct subtypes of PTSD.