Efstathios D. Gotsis

Noninvasive Histologic Grading of Solid Astrocytomas Using Proton Magnetic Resonance Spectroscopy

Background: Proton magnetic resonance spectroscopy (1H MRS) constitutes a promising modality to assess intracranial pathology. We present our experience using this method in grading solid brain astrocytomas. Material and Methods: Using a 1.5-Tesla MRI unit, 71 patients with the radiographic diagnosis of astrocytoma were examined. Water-suppressed single-voxel 1H MRS was employed in all of our patients. The concentrations of choline (Cho), N-acetyl-aspartate (NAA), phosphocreatine-creatine (Pcr-Cr), myo-inositol (MI), lactate (Lac), lipids (Lip) as well as the metabolite ratios of Cho/Pcr-Cr, NAA/PCr-Cr and NAA/Cho were calculated. An appropriate surgical biopsy was performed. Standard pathology examination was employed in a double-blinded fashion. Results: An increased concentration of Cho and decreased concentrations of Pcr-Cr and NAA were detected. The concentrations of Lac, Lip and MI varied inconsistently, even among tumors of the same histologic grade. The Cho/Pcr-Cr ratio was calculated. This ratio was found to be 2.15 ± 0.26 in 27 patients with astrocytomas grade I and II, 2.78 ± 0.09 in 18 patients with grade III, and 5.40 ± 0.16 in 26 patients with grade IV. Discussion: The increased concentration of Cho is due to the increased cellularity and a relatively increased number of membranous structures in highly malignant tumors. In abnormal anaerobic metabolic tumor states there is relatively less phosphorylization of creatine. By using the Cho/Pcr-Cr ratio the concomitant effects of structural and metabolic alteration can thereby be emphasized for diagnostic advantage. Conclusion: The Cho/Pcr-Cr is a very important and statistically significant marker (p = 0.043) determining the degree of intracranial astrocytoma malignancy.

Magnetic resonance evaluation of liver and myocardial iron deposition in thalassemia intermedia and b-thalassemia major

Introduction b-Thalassemia major (TM) and thalassemia intermedia (TI) are forms of inherited hemoglobinopathies. Our aim was to evaluate a population of asymptomatic TM and TI patients using cardiovascular magnetic resonance (CMR). We hypothesized that the TI group could be differentiated from the TM group based on T2*. We also hypothesized that the TI group would demonstrate significantly higher cardiac output compared to the TM group. Patients and methods Twenty-one consecutive TI patients aged 23(19–25) years, 21 TM patients and 21 age and sex matched controls were studied. Evaluation of heart, liver T2* relaxation time and right and left ventricular parameters was performed using a 1.5 T system. Results Myocardial and liver T2* values were significantly higher in TI patients compared to TM (34.35 ± 2.36 vs 15.77 ± 3.53 m, P < 0.001 and 5.12 ± 6.52 vs 1.36 ± 0.53 ms, P < 0.001, respectively). Controls had myocardial T2* 35.07 ± 4.52 ms (similar to TI patients, but significantly increased compared to TM patients, P < 0.001) and liver T2* 26.28 ± 2.37 ms (significantly increased compared to both TI and TM patients, P < 0.001). Left ventricular end-diastolic (LVEDV), end-systolic (LVESV) volumes and left ventricular ejection fraction (LVEF) were higher in TI patients compared to TM (P < 0.001). Stroke volume (LVSV), cardiac output (LVCO) and cardiac index (LVCI) were similarly increased in TI patients compared to TM (P < 0.001). Right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV) and right ventricular ejection fraction (RVEF) were higher in TI patients compared to TM (P < 0.001). Conclusions Although in TM iron plays a crucial role in the evolution of the disease, in TI the high output cardiac state seems to be the most prominent finding.

The role of proton magnetic resonance spectroscopy in the diagnosis and categorization of cerebral abscesses

Despite recent advances in neuroimaging, differentiation between cerebral abscesses and necrotic tumors with ring-type contrast enhancement can be puzzling at times. The introduction of advanced imaging techniques, such as diffusion-weighted imaging, has contributed to the identification of cerebral abscesses. However, differentiation may be impossible with imaging only. In this review the authors evaluate the role of proton magnetic resonance (MR) spectroscopy in differentiating between cerebral abscesses and necrotic tumors and address the spectral characteristics of intracranial abscesses. A large number of metabolites not detected in the normal brain spectra may be detected and give valuable information regarding the nature of the abscesses. Proton MR spectroscopy is a safe, noninvasive diagnostic modality, which could significantly increase the accuracy and specificity of conventional MR imaging in differentiating between malignant tumors and cerebral abscesses and provide valuable information regarding the cause of an abscess, as well as, its response to the chosen treatment.

Preoperative Evaluation with fMRI of Patients with Intracranial Gliomas

Introduction. Aggressive surgical resection constitutes the optimal treatment for intracranial gliomas. However, the proximity of a tumor to eloquent areas requires exact knowledge of its anatomic relationships to functional cortex. The purpose of our study was to evaluate fMRIs accuracy by comparing it to intraoperative cortical stimulation (DCS) mapping. Material and Methods. Eighty-seven patients, with presumed glioma diagnosis, underwent preoperative fMRI and intraoperative DCS for cortical mapping during tumor resection. Findings of fMRI and DCS were considered concordant if the identified cortical centers were less than 5 mm apart. Pre and postoperative Karnofsky Performance Scale and Spitzer scores were recorded. A postoperative MRI was obtained for assessing the extent of resection. Results. The areas of interest were identified by fMRI and DCS in all participants. The concordance between fMRI and DCS was 91.9% regarding sensory-motor cortex, 100% for visual cortex, and 85.4% for language. Data analysis showed that patients with better functional condition demonstrated higher concordance rates, while there also was a weak association between tumor grade and concordance rate. The mean extent of tumor resection was 96.7%. Conclusions. Functional MRI is a highly accurate preoperative methodology for sensory-motor mapping. However, in language mapping, DCS remains necessary for accurate localization.

Temporal pole proton preoperative magnetic resonance spectroscopy in patients undergoing surgery for mesial temporal sclerosis

OBJECT The purpose of this prospective study was to compare the results of proton MR spectroscopy (MRS) in temporal poles in patients with unilateral mesial temporal sclerosis (MTS) with the histopathological findings of the resected temporal poles. METHODS A total of 23 patients (14 male and 9 female) with a mean age of 25.2 years (range 17-45 years) were included in this study, which was conducted over a 4-year period. All patients suffered medically refractory epilepsy due to unilateral, MRI-proven MTS, with no other imaging abnormalities. All participants underwent preoperative single-voxel proton MRS using a 3-T MRI unit. The hippocampi and temporal poles were examined bilaterally. The concentrations of N-acetyl-aspartate (NAA), choline (Cho), and creatine (Cr) were measured, and the NAA/Cho, NAA/Cr, and NAA/Cho+Cr ratios were calculated. All patients underwent anterior temporal lobectomy and ipsilateral amygdalohippocampectomy, and surgical specimens from the temporal poles were sent for histopathological examination. Comparisons of the spectroscopic and histopathological results of the resected temporal poles were performed. The modified Engel classification system was used for evaluating seizure outcome in the cohort. RESULTS The preoperative spectroscopic profiles of the sclerotic hippocampi were abnormal in all patients, and the contralateral hippocampus showed altered spectroscopic findings in 12 patients (52.2%). Spectroscopy of the temporal poles demonstrated severely decreased concentrations of NAA, markedly increased concentrations of Cho, and increased concentrations of Cr in the temporal pole ipsilateral to the MTS in 15 patients (65.2%). Similarly, the NAA/Cho, NAA/Cr, and NAA/Cho+Cr ratios were severely decreased in the temporal pole ipsilateral to the MTS in 16 patients (69.6%). Histopathological examination of the resected temporal poles demonstrated ischemic changes in 5 patients (21.7%), gliotic changes in 4 (17.4%), demyelinating changes in 3 (13.0%), and microdysplastic changes in 1 patient (4.3%). Comparisons of the spectroscopic and histopathological findings showed that the sensitivity of proton MRS was 100%, its specificity was 80%, its positive predictive value was 87%, and its negative predictive value was 100%. The mean follow-up time in this study was 3.4 years. At the end of the 2nd postoperative year, 17 patients (73.9%) were in Engel Class I, 5 (21.7%) were in Class II, and 1 (4.3%) was in Class III. CONCLUSIONS Proton MRS detected altered ipsilateral temporal pole metabolism in patients with unilateral MTS. These metabolic changes were associated with permanent histological abnormalities of the temporal pole. This finding demonstrates that MTS may be a more diffuse histological process, and exact preoperative knowledge of its temporal extent becomes of paramount importance in the selection of the best surgical approach in these patients. Further validation of the observations is necessary for defining the role of temporal pole proton MRS in cases of temporal lobe epilepsy.

The Role of Functional MRI in Intracranial Glioma Resection

It is generally accepted that tumor extirpation constitutes the treatment goal in cases of intracranial tumors. It is also well known that intracranial gliomas are infiltrative lesions with ill-defined borders, and their total resection is often quite challenging. Moreover, the presence of a glioma in an eloquent cortical area may make its extirpation even more difficult. It has been demonstrated that extensive glioma resection is associated with prolonged survival and better quality of life, and the overall outcome of patients with intracranial gliomas is associated with the extent of the tumor’s surgical resection [Lacroix et al., 2001; McDonald et al., 1999; National Comprehensive Cancer Network, 2007; Sanai & Berger, 2008; Stafford et al., 1998). Therefore, every effort to achieve maximal tumor resection without jeopardizing vital neuronal functions becomes of paramount importance in cases of intracranial gliomas. Exact knowledge of the cortical topography, accurate identification of all eloquent cortical areas as well as delineation of their relationships with the tumor, constitute key elements in avoiding all functional cortical areas, while aggressive tumor resection is accomplished. It is well known that conventional imaging studies providing pure structural anatomical information are not sufficient for identifying and localizing functional cortical areas, since there are frequent anatomical variations, and cortical functional center shift due to brain distortion and plasticity, particularly in glioma cases. Various methodologies have been developed for identifying different functional areas of the cerebral cortex and accurately localize them, in regard to the studied tumor on each individual case. Intraoperative electrophysiological studies such as recording of Somato-Sensory Evoked Potentials (SSEPs), Motor Evoked Potentials (MEPs), Direct Cortical Stimulation (DCS), and spontaneous Electro-Myo-Graphy (sEMG) are considered the gold standard for cortical mapping and delineation of functional cortical networks. The major drawback of these methodologies however, is the fact that all are invasive tests and cannot provide all this valuable information preoperatively. Thus, the development of non-invasive tests for cortical mapping seems to be mandatory. Recently, advanced imaging and electrophysiological studies such as Positron Emission Tomography (PET), brain SPECT imaging, functional

The Role of Magnetic Resonance Spectroscopy in the Diagnosis of Ring Enhancing Lesions

Ring-enhancing intracranial lesions constitute a common and quite puzzling diagnostic dilemma. These lesions may present as solitary or multiple on a routine brain MRI, and are characterized by a contrast enhancing halo and a non enhancing center. The central part may present with low signal intensity on T1, and high signal intensity on T2 weighted images. They are usually surrounded by a variable amount of edema. They may be located anywhere in the brain, although the junctional zone of gray-white matter is their most common location [Omuroet al., 2006; Smirniotopoulos et al., 2007]. Their size may vary from a few millimetres to several centimetres. The differential diagnosis of ring enhancing lesions is quite large. It may include neoplasms, infections, inflammatory processes, or vascular pathologies. The incidence of each pathological entity depends highly on the geographical region and the study population. It is well documented that infections and inflammatory processes are more common in developing countries, while neoplasms and demyelinating lesions are more frequent in developed countries. Clinical history is not always helpful in their differential diagnosis, since more than 50% of CNS infections may present without fever and no obvious inflicting incident. Moreover, other laboratory tests may not be able to help in their differential diagnosis. In addition, the presenting symptomatology and the clinical examination of these patients are non-specific and frequently overlapping, making thus the establishment of an accurate diagnosis quite difficult. Routine brain MR imaging is very sensitive in the identification of ring enhancing lesions but it cannot distinguish between neoplastic and non neoplastic lesions, in a large percentage of these cases. Frequently, the differentiation of a tumor from an infection is quite difficult, based solely on conventional MRI. Therefore, advanced MR imaging