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 fMRI's 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.

Effect of deferiprone or deferoxamine on right ventricular function in thalassemia major patients with myocardial iron overload.

BACKGROUND: Thalassaemia major (TM) patients need regular blood transfusions that lead to accumulation of iron and death from heart failure. Deferiprone has been reported to be superior to deferoxamine for the removal of cardiac iron and improvement in left ventricular (LV) function but little is known of their relative effects on the right ventricle (RV), which is being increasingly recognised as an important prognostic factor in cardiomyopathy. Therefore data from a prospective randomised controlled trial (RCT) comparing these chelators was retrospectively analysed to assess the RV responses to these drugs. METHODS: In the RCT, 61 TM patients were randomised to receive either deferiprone or deferoxamine monotherapy, and CMR scans for T2* and cardiac function were obtained. Data were re-analysed for RV volumes and function at baseline, and after 6 and 12 months of treatment. RESULTS: From baseline to 12 months, deferiprone reduced RV end systolic volume (ESV) from 37.7 to 34.2 mL (p=0.008), whilst RV ejection fraction (EF) increased from 69.6 to 72.2% (p=0.001). This was associated with a 27% increase in T2* (p<0.001) and 3.1% increase in LVEF (p<0.001). By contrast, deferoxamine showed no change in RVESV (38.1 to 39.1 mL, p=0.38), or RVEF (70.0 to 69.9%, p=0.93) whereas the T2* increased by 13% (p<0.001), but with no change in LVEF (0.32%; p=0.66). Analysis of between drugs treatment effects, showed significant improvements favouring deferiprone with a mean effect on RVESV of -1.82 mL (p=0.014) and 1.16% for RVEF (p=0.009). Using regression analysis the improvement in RVEF at 12 months was shown to be greater in patients with lower baseline EF values (p<0.001), with a significant difference in RVEF of 3.5% favouring deferiprone over deferoxamine (p=0.012). CONCLUSION: In this retrospective analysis of a prospective RCT, deferiprone monotherapy was superior to deferoxamine for improvement in RVEF and end-systolic volume. This improvement in the RV volumes and function may contribute to the improved cardiac outcomes seen with deferiprone.

Cardiac magnetic resonance in transfusion dependent thalassaemia: assessment of iron load and relationship to left ventricular ejection fraction.

Cardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in the determination of transfusional cardiac iron overload in patients with thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with respect to cardiac dysfunction (CD) as determined by CMR-derived left ventricular ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were recorded in 303 patients with thalassaemia major, at the time of their first CMR. T2* was correlated with LVEF (regression coefficient: 0·57, P<0·001). The prevalence of CD was 32·9% in patients with T2*≤8 ms, 12·5% in patients with T2*>8 ms and ≤14 ms and reduced to 9·1% in patients with T2* between 14-20 ms. As the probability of CD is progressively, and not suddenly, reduced with increasing values of T2*, CMR has a limited diagnostic value for CD (Receiver operating characteristic analysis, area under the curve = 0·68). Patients with cardiac T2*≤8 ms require careful and intensive management. This risk decreases with increasing values of T2* but even in mildly loaded patients the probability of impaired LVEF is not negligible.

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.

The uses and differences of r2 and r2* in the determination of iron overload in iron loaded thalassemia patients.

Early attempts to use magnetic resonance imaging (MRI) for assessing iron overload in beta-thalassemia (thal) patients began more than 20 years ago. With advances in MRI, more quantitative efforts focused on measuring transverse relaxation time rates (R2 and R2*) of the liver and/or myocardium. Recently, calibration curves of R2 and R2* were reported that allowed one to determine the absolute concentrations of iron in the liver, provided that R2 and R2* were determined with the same technique. The difficulty of obtaining sufficient myocardium biopsy samples has prevented similar calibration curves being reported for the myocardium. Preliminary data indicate that liver and myocardium R2* vs. R2 plots are similar over a large range of R2* and R2 values. Obviously, myocardium biopsy samples are needed to confirm whether myocardium R2* and R2 plots vs. iron concentration are similar to those published for the liver. The various methods for determining R2 and R2* are discussed. It is suggested to use both R2* and R2 for assessing iron overload in the liver and myocardium.

Cardiac magnetic resonance imaging R2* assessments and analysis of historical parameters in patients with transfusion-dependent thalassemia.

Recent advances in magnetic resonance imaging (MRI) techniques allow the assessment of iron overload in tissues 1 especially the heart, 2 in transfusion-dependent thalassemia patients. The R2* value (1/T2*) recorded in the intraventricular septum of the heart indirectly measures the degree of cardiac iron load. Applying this new technology we looked at a number of historical and biochemical parameters in order to determine their relationship to cardiac iron overload and the effect of cardiac iron on functional and structural changes of the heart in transfusion-dependent thalassemics.

Myocardial and hepatic T2* magnetic resonance evaluation in ex-thalassemic patients after bone-marrow transplantation.

Bone marrow transplantation (BMT) is the only complete cure for b-thalassemia. Iron depletion therapy is still required to remove excess iron, accumulated before BMT. Hepatic and myocardial iron load were evaluated using T2* magnetic resonance in 8 ex-thalassemic patients after BMT, aged 19.5 +/- 4.25 years, who were in iron depletion therapy. Average hepatic T2* was 18.8 +/- 11.0 msec (4.1-35.0 msec). In 4 out of 8 patients iron overload was detected, not exceeding however 4 mg/gr dry tissue. Average heart T2* was 31.0 +/- 4.6 msec (25.6-35.2 msec), not significantly different (P = 0.18) from our age-matched normal population (33.0 +/- 4.0). Normal left ventricular ejection fraction was found in 7 out of 8 patients (mean 64.5 +/- 7.0%) with the remaining having a marginal value of 54.1%. Ferritin level before BMT was 1748 +/- 451 mug/l and dropped to 536 +/- 260 microg/l at the end of iron depletion therapy after BMT. Current ferritin level was 271 +/- 253 microg/l and although it was significant lower compared to both ferritin before BMT (P < 0.001) and after iron depletion (P < 0.001), evidence of residual hepatic iron load was identified by T2*. Hepatic and myocardial T2* magnetic resonance can be used as a more reliable index than ferritin for evaluation of iron depletion therapy in ex-thalassemic patients after BMT.

Brain natriuretic peptide as marker of myocardial iron load in beta-thalassemia.

Cardiomyopathy due to iron overload represents a frequent life-limiting complication in patients with beta-thalassemia major. We have conducted a study which proved that brain natriuretic peptide plasma levels have high sensitivity and negative predictive value in detecting cardiac hemosiderosis.

Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis.

Most deaths in beta-thalassemia major result from cardiac complications due to iron overload. Differential effects on myocardial siderosis may exist between different chelators. A randomized controlled trial was performed in 61 patients previously maintained on subcutaneous deferoxamine. The primary end point was the change in myocardial siderosis (myocardial T2(*)) over 1 year in patients maintained on subcutaneous deferoxamine or those switched to oral deferiprone monotherapy. The dose of deferiprone was 92 mg/kg/d and deferoxamine was 43 mg/kg for 5.7 d/wk. Compliance was 94% +/- 5.3% and 93% +/- 9.7% (P = .81), respectively. The improvement in myocardial T2(*) was significantly greater for deferiprone than deferoxamine (27% vs 13%; P = .023). Left ventricular ejection fraction increased significantly more in the deferiprone-treated group (3.1% vs 0.3% absolute units; P = .003). The changes in liver iron level (-0.93 mg/g dry weight vs -1.54 mg/g dry weight; P = .40) and serum ferritin level (-181 microg/L vs -466 microg/L; P = .16), respectively, were not significantly different between groups. The most frequent adverse events were transient gastrointestinal symptoms for deferiprone-treated patients and local reactions at the infusion site for deferoxamine. There were no episodes of agranulocytosis. Deferiprone monotherapy was significantly more effective than deferoxamine over 1 year in improving asymptomatic myocardial siderosis in beta-thalassemia major.

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.