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Article: Whole-Brain Analysis of Amyotrophic Lateral Sclerosis by Using Echo-Planar Spectroscopic Imaging.
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ABSTRACT: Purpose:To detect regional metabolic differences in amyotrophic lateral sclerosis (ALS) with whole-brain echo-planar spectroscopic imaging.Materials and Methods:Sixteen patients with ALS (nine men, seven women; mean age, 56.6 years), five persons suspected of having ALS (four men, one woman; mean age, 62.6 years), and 10 healthy control subjects (five men, five women; mean age, 56.1 years) underwent echo-planar spectroscopic imaging after providing informed consent. The study was approved by the institutional review board and complied with HIPAA. Data were analyzed with the Metabolic Imaging and Data Analysis System software, and processed metabolite maps were coregistered and normalized to a standard brain template. Metabolite maps of creatine (Cr), choline (Cho), and N-acetylaspartate (NAA) were segmented into 81 regions with Automated Anatomical Labeling software to measure metabolic changes throughout the brains of patients with ALS. Statistical analysis involved an unpaired, uncorrected, two-sided Student t test.Results:The NAA/Cho ratio across six regions was significantly lower by a mean of 23% (P ≤ .01) in patients with ALS than in control subjects. These regions included the caudate, lingual gyrus, supramarginal gyrus, and right and left superior and right inferior occipital lobes. The NAA/Cr ratio was significantly lower (P ≤ .01) in eight regions in the patient group, by a mean of 16%. These included the caudate, cuneus, frontal inferior operculum, Heschl gyrus, precentral gyrus, rolandic operculum, and superior and inferior occipital lobes. The Cho/Cr ratio did not significantly differ in any region between patient and control groups.Conclusion:Whole-brain echo-planar spectroscopic imaging permits detection of regional metabolic abnormalities in ALS, including not only the motor cortex but also several other regions implicated in ALS pathophysiologic findings.© RSNA, 2013.Radiology 01/2013; · 5.73 Impact Factor -
Article: Pretreatment diffusion-weighted and dynamic contrast-enhanced MRI for prediction of local treatment response in squamous cell carcinomas of the head and neck.
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ABSTRACT: The objective of our study was to predict response to chemoradiation therapy in patients with head and neck squamous cell carcinoma (HNSCC) by combined use of diffusion-weighted imaging (DWI) and high-spatial-resolution, high-temporal-resolution dynamic contrast-enhanced MRI (DCE-MRI) parameters from primary tumors and metastatic nodes. Thirty-two patients underwent pretreatment DWI and DCE-MRI using a modified radial imaging sequence. Postprocessing of data included motion-correction algorithms to reduce motion artifacts. The median apparent diffusion coefficient (ADC), volume transfer constant (K(trans)), extracellular extravascular volume fraction (v(e)), and plasma volume fraction (v(p)) were computed from primary tumors and nodal masses. The quality of the DCE-MRI maps was estimated using a threshold median chi-square value of 0.10 or less. Multivariate logistic regression and receiver operating characteristic curve analyses were used to determine the best model to discriminate responders from nonresponders. Acceptable χ(2) values were observed from 84% of primary tumors and 100% of nodal masses. Five patients with unsatisfactory DCE-MRI data were excluded and DCE-MRI data for three patients who died of unrelated causes were censored from analysis. The median follow-up for the remaining patients (n = 24) was 23.72 months. When ADC and DCE-MRI parameters (K(trans), v(e), v(p)) from both primary tumors and nodal masses were incorporated into multivariate logistic regression analyses, a considerably higher discriminative accuracy (area under the curve [AUC] = 0.85) with a sensitivity of 81.3% and specificity of 75% was observed in differentiating responders (n = 16) from nonresponders (n = 8). The combined use of DWI and DCE-MRI parameters from both primary tumors and nodal masses may aid in prediction of response to chemoradiation therapy in patients with HNSCC.American Journal of Roentgenology 01/2013; 200(1):35-43. · 2.78 Impact Factor -
Article: Frontal lobe abnormalities on MRS correlate with poor letter fluency in ALS.
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ABSTRACT: To examine whether frontal lobe abnormalities on magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis (ALS) correlate with poor letter fluency (LF). Twenty-five patients with ALS (20 with definite, probable, or possible ALS and 5 with progressive muscular atrophy) performed an LF task, involving F word generation in 1 minute, and underwent MRS. Comparisons were made between patients with ALS with impaired LF and unimpaired LF based on an empirically derived cutoff score. A Spearman correlation was performed between the patient's N-acetyl acetate/creatinine-phosphocreatinine ratio (NAA/Cr) and the number of F words generated. LF was impaired in 50% of patients with ALS. Patients with impaired LF had reduced NAA/Cr in the DLPFC compared with those with unimpaired LF (p = 0.007). There was a significant correlation between LF and NAA/Cr in the DLPFC (r = 0.51, p = 0.0009). The ALS Functional Rating Scale score, clinical region of motor onset, and disease category had no effect on LF or NAA/Cr in the DLPFC. A reduced NAA/Cr in the DLPFC of patients with ALS is a marker of neuronal dysfunction and correlates with impaired performance on a clinical measure of executive function.Neurology 07/2012; 79(6):583-8. · 8.31 Impact Factor -
Article: Magnetic resonance perfusion-weighted imaging defines angiogenic subtypes of oligodendroglioma according to 1p19q and EGFR status
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ABSTRACT: 1p19q LOH has been shown to predict radio- and chemosensitivity and prolonged survival in oligodendrogliomas (OLs). We have recently shown that magnetic resonance perfusion-weighted imaging (MR-PWI) may be useful in predicting the histopathological grade or cytogenetic type of oligodendroglial neoplasms. MR-PWI allows noninvasive determination of relative tumor blood volume (rTBV), which may reflect the degree of neoplastic angiogenesis and metabolism. The present study was aimed to correlate rTBV to the angiogenic markers and EGFR expression in oligodendroglial tumors with 1p/19q LOH or 1p LOH (Group 1) and 1p19q intact alleles or 19q LOH (Group 2), respectively. In WHO grade II neoplasms, Group 1 showed significantly greater rTBV than Group 2 (P=0.013). However, the differences between Group 1 and Group 2 were not significant in grade III tumors. Probe-based real-time RT-PCR analyses showed that 12% of Group 2 high-grade tumors with intact 1p19q exhibited dramatic EGFR overexpression (designated EGFR-high). Grade III neoplasms showed a significantly higher rTBV than grade II neoplasms. Group 1 tumors showed significantly higher rTBV than Group 2 tumors, independent of the EGFR-high subtype. Real-time RT-PCR analyses showed increased expression of VEGF, CD31 and CD105 in Group 1 tumors as compared to Group 2 tumors, excluding the EGFR-high subtype. Multivariable linear regression analysis showed a significant association of rTBV with 1p19q LOH, and expression of EGFR and VEGF. Therefore, the combined use of extensive molecular profiling and advanced MR imaging modalities may improve the accuracy of tumor grading, provide prognostic information, and has the potential to influence treatment decisions.Journal of Neuro-Oncology 04/2012; 92(3):373-386. · 3.21 Impact Factor -
Article: Use of magnetic perfusion-weighted imaging to determine epidermal growth factor receptor variant III expression in glioblastoma.
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ABSTRACT: Identification of the epidermal growth factor receptor variant III (EGFRvIII) mutation in glioblastoma has become increasingly relevant in the optimization of therapy. Traditionally, determination of tumor EGFRvIII-expression has relied on tissue-based diagnostics. Here, we assess the accuracy of magnetic resonance perfusion-weighted imaging (MR-PWI) in discriminating the EGFRvIII-expressing glioblastoma subtype. We analyzed RNA from 132 primary human glioblastoma tissue samples by reverse-transcription polymerase chain reaction (RT-PCR) for the EGFRvIII and EGFR wild-type mutations and by quantitative RT-PCR for expression of vascular endothelial growth factor (VEGF). Concurrently, 3 independent observers reviewed preoperative 1.5-Tesla (T)/SE or 3.0-Tesla (T)/GE MR perfusion images to determine the maximum relative tumor blood volume (rTBV) of each of these tumors. EGFRvIII-expressing glioblastomas showed significantly higher rTBV, compared with those tumors lacking EGFRvIII expression. This association was observed in both the 1.5T/SE (P = .000) and 3.0T/GE (P = .001) cohorts. By logistic regression analysis, combining the 2 MR system cohorts, rTBV was a very strong predictor of EGFRvIII mutation (odds ratio [rTBV] = 2.70; P = .000; McFadden's ρ(2) = 0.23). Furthermore, by receiver-operating characteristic curve analysis, rTBV discriminated EGFRvIII with very high accuracy (A(z) = 0.81). In addition, we found that VEGF upregulation was associated, although without reaching statistical significance, with EGFRvIII expression (P = .16) and with increased rTBV (F-ratio = 2.71; P = .102). These trends suggest that VEGF-mediated angiogenesis may be a potential mediator of angiogenesis to increase perfusion in EGFRvIII-expressing glioblastomas, but there are likely several other contributing factors. This study demonstrates the potential to use rTBV, a MR-PWI-derived parameter, as a noninvasive surrogate of the EGFRvIII mutation.Neuro-Oncology 04/2012; 14(5):613-23. · 5.72 Impact Factor
