Diana Gomez-Hassan

BDNF Val66Met Allele Is Associated with Reduced Hippocampal Volume in Healthy Subjects

BACKGROUND A frequent polymorphism of the brain-derived neurotrophic factor (BDNF) gene (val(66)met) has been suggested to modulate hippocampal neuronal plasticity and has been associated with individual variations in emotional reactivity traits and episodic memory. METHODS The hippocampal formation was outlined in high-resolution anatomical magnetic resonance imaging (MRI) data in a sample of 36 healthy volunteers and compared between individuals as a function of the presence of the met-BDNF allele. Both whole-brain volume corrected and uncorrected data were tested for effects of genotype, sex, and age. RESULTS The met-BDNF allele was associated with an 11% reduction in the volume of the hippocampal formation. CONCLUSIONS In spite of a relatively small sample size, the presence of the met-BDNF allele was found associated with a reduced volume of the hippocampal formation in healthy volunteers and may represent a vulnerability factor for the development of disease processes associated with the dysfunction of this brain region.

Diffusion Tensor Imaging of the Brain. Review of clinical applications

We review the theoretical background to diffusion tensor imaging (DTI) and some of its commoner clinical applications, such as cerebral ischemia, brain maturation and traumatic brain injury. We also review its potential use in diseases such as epilepsy, multiple sclerosis, and Alzheimer’s disease. The value of DTI in the investigation of brain tumors and metabolic disorders is assessed.

Clinical applications of diffusion tensor imaging.

Directionally‐ordered cellular structures that impede water motion, such as cell membranes and myelin, result in water mobility that is also directionally‐dependent. Diffusion tensor imaging characterizes this directional nature of water motion and thereby provides structural information that cannot be obtained by standard anatomic imaging. Quantitative apparent diffusion coefficients and fractional anisotropy have emerged from being primarily research tools to methods enabling valuable clinical applications. This review describes the clinical utility of diffusion tensor imaging, including the basic principles of the technique, acquisition, data analysis, and the major clinical applications. J. Magn. Reson. Imaging 2004;19:6–18.

Association of 11C-Methionine PET Uptake With Site of Failure After Concurrent Temozolomide and Radiation for Primary Glioblastoma Multiforme

PURPOSE To determine whether increased uptake on 11C-methionine-PET (MET-PET) imaging obtained before radiation therapy and temozolomide is associated with the site of subsequent failure in newly diagnosed glioblastoma multiforme (GBM). METHODS Patients with primary GBM were treated on a prospective trial with dose- escalated radiation and concurrent temozolomide. As part of the study, MET-PET was obtained before treatment but was not used for target volume definition. Using automated image registration, we assessed whether the area of increased MET-PET activity (PET gross target volume [GTV]) was fully encompassed within the high-dose region and compared the patterns of failure for those with and without adequate high-dose coverage of the PET-GTV. RESULTS Twenty-six patients were evaluated with a median follow-up of 15 months. Nineteen of 26 had appreciable (>1 cm(3)) volumes of increased MET-PET activity before treatment. Five of 19 patients had PET-GTV that was not fully encompassed within the high-dose region, and all five patients had noncentral failures. Among the 14 patients with adequately covered PET-GTV, only two had noncentral treatment failures. Three of 14 patients had no evidence of recurrence more than 1 year after radiation therapy. Inadequate PET-GTV coverage was associated with increased risk of noncentral failures. (p < 0.01). CONCLUSION Pretreatment MET-PET appears to identify areas at highest risk for recurrence for patients with GBM. It would be reasonable to test a strategy of incorporating MET-PET into radiation treatment planning, particularly for identifying areas for conformal boost.

Concurrent Temozolomide and Dose-Escalated Intensity Modulated Radiation Therapy in Newly Diagnosed Glioblastoma

Purpose: To determine the maximum-tolerated dose (MTD) of radiation (RT) with concurrent temozolomide in patients with newly diagnosed glioblastoma (GBM), to estimate their progression-free (PFS) and overall survival (OS), and to assess the role of 11C methionine PET (MET-PET) imaging in predicting recurrence. Experimental Design: Intensity-modulated RT (IMRT) doses of 66 to 81 Gy, assigned to patients by the time-to-event continual reassessment method, were delivered over 6 weeks with concurrent daily temozolomide (75 mg/m2) followed by adjuvant cyclic temozolomide (200 mg/m2 d1-5 q28d ×6 cycles). Treatment was based on gadolinium-enhanced MRI. Pretreatment MET-PET scans were obtained for correlation with eventual sites of failure. Results: A total of 38 patients were analyzed with a median follow-up of 54 months for patients who remain alive. Late CNS grade ≥III toxicity was observed at 78 (2 of 7 patients) and 81 Gy (1 of 9 patients). None of 22 patients receiving 75 or less Gy developed RT necrosis. Median OS and PFS were 20.1 (14.0–32.5) and 9.0 (6.0–11.7) months, respectively. Twenty-two of 32 patients with pretreatment MET-PET uptake showed uptake beyond the contrast-enhanced MRI. Patients whose treatment did not include the region of increased MET-PET uptake showed an increased risk of noncentral failure (P < 0.001). Conclusions: Patients with GBM can safely receive standard temozolomide with 75 Gy in 30 fractions, delivered using IMRT. The median OS of 20.1 months is promising. Furthermore, MET-PET appears to predict regions of high risk of recurrence not defined by MRI, suggesting that further improvements may be possible by targeting metabolically active regions. Clin Cancer Res; 18(1); 273–9. ©2011 AACR.

Sodium methohexital (brevital) as an anesthetic in the Wada test.

Summary:  Purposes: We report our experience with sodium methohexital (Brevital) as an anesthetic used in the Wada test for language and memory in 86 epilepsy surgery patients (173 procedures).

MR spectroscopy in the evaluation of recurrent contrast-enhancing lesions in the posterior fossa after tumor treatment

Recurrent contrast-enhancing lesions arising within foci of prior brain neoplasms treated with chemotherapy and/or radiation therapy pose a significant diagnostic dilemma, as they may represent recurrent or residual tumor, treatment-related changes, or a combination of both. Those lesions specifically in the posterior fossa are even more difficult to assess, given the technical limitations of 2D CSI in the infratentorial compartment. We explored the feasibility of 2D-CSI MR spectroscopy in the evaluation of recurrent contrast-enhancing lesions in eight consecutive patients who had undergone treatment for posterior fossa or brainstem tumors. Mean Cho/Cr (choline/creatine) ratios obtained by 2D-CSI in recurrent tumor, treatment-related changes, and normal white matter were 2.93, 1.62, and 0.97, respectively, mean Cho/NAA (choline/N-Acetyl aspartate) ratios were 4.34, 1.74, and 0.93, and mean NAA/Cr (N-acetyl aspartate/creatine) ratios were 0.74, 0.92, and 1.26, respectively. In conclusion, also in the posterior fossa, MR spectroscopy is likely to be useful as an adjunct to conventional imaging characteristics in distinguishing recurrent tumor from treatment-related changes, irrespectively of the MRS technique used. In most cases spectra of diagnostic quality can be obtained using 2D-CSI to include coverage of both the lesion and its vicinity.

Investigation of the diffusion abnormality index as a new imaging biomarker for early assessment of brain tumor response to radiation therapy

BACKGROUND Diffusion MRI, although having the potential to be a biomarker for early assessment of tumor response to therapy, could be confounded by edema and necrosis in or near the brain tumors. This study aimed to develop and investigate the ability of the diffusion abnormality index (DAI) to be a new imaging biomarker for early assessment of brain metastasis response to radiation therapy (RT). METHODS Patients with either radiosensitive or radioresistant brain metastases that were treated by whole brain RT alone or combined with bortezomib as a radiation sensitizer had diffusion-weighted (DW) MRI pre-RT and 2 weeks (2W) after starting RT. A patient-specific diffusion abnormality probability function (DAProF) was created to account for abnormal low and high apparent diffusion coefficients differently, reflecting respective high cellularity and edema/necrosis. The DAI of a lesion was then calculated by the integral of DAProF-weighted tumor apparent diffusion coefficient histogram. The changes in DAI from pre-RT to 2W were evaluated for differentiating the responsive, stable, and progressive tumors and compared with the changes in gross tumor volume and conventional diffusion metrics during the same time interval. RESULTS In lesions treated with whole brain RT, the DAI performed the best among all metrics in predicting the posttreatment response of brain metastases to RT. In lesions treated with whole brain RT + bortezomib, although DAI was the best predictor, the performance of all metrics worsened compared with the first group. CONCLUSIONS The ability of DAI for early assessment of brain metastasis response to RT depends upon treatment regimes.

Seizure semiology and neuroimaging findings in patients with midline spikes.

Summary:  Purpose: Midline epileptiform discharges are rare compared with discharges at other scalp locations. Neuroimaging results and semiologic seizure characteristics of patients with midline spikes are not adequately described. The aim of this study was to describe the neuroimaging findings and detailed seizure semiologies in patients with midline spikes.

MRI Findings in Spinal MRI of 306 Children with Scoliosis. A Comprehensive Retrospective Analysis.

The aim of this study was to analyze the MRI findings and assess the prevalence of different associated structural abnormalities in children with scoliosis and to determine if the age of onset is a possible indicator of intraspinal pathology. This is a retrospective analysis of 663 consecutive MR examinations (319 patients). Thirteen patients with known intraspinal tumors were excluded and a total of 306 patients aged 2–18 years with scoliosis were subjected for analysis. The scoliosis was regarded as idiopathic in 62% of patients. Among the remaining 38% the most commonly seen abnormality was syrinx and Chiari malformations. There was no statistically significant difference in the occurrence of syrinx only or syrinx associated with Chiari I malformation in patients younger than ten years and those older than ten years. MRI examination is an essential part of the work up of scoliosis in the pediatric population especially before any corrective surgery. This study and a review of the current literature suggest there is no clinical marker that would definitely serve as an indicator of the presence of intraspinal pathology in these patients.