Ioannis Fezoulidis

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.

Differentiation of glioblastoma multiforme from metastatic brain tumor using proton magnetic resonance spectroscopy, diffusion and perfusion metrics at 3 T

Abstract Purpose: To assess the contribution of 1H-magnetic resonance spectroscopy (1H-MRS), diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI) and dynamic susceptibility contrast-enhanced (DSCE) imaging metrics in the differentiation of glioblastomas from solitary metastasis, and particularly to clarify the controversial reports regarding the hypothesis that there should be a significant differentiation between the intratumoral and peritumoral areas. Methods: Conventional MR imaging, 1H-MRS, DWI, DTI and DSCE MRI was performed on 49 patients (35 glioblastomas multiforme, 14 metastases) using a 3.0-T MR unit. Metabolite ratios, apparent diffusion coefficient (ADC), fractional anisotropy (FA) and relative cerebral blood volume (rCBV) were measured in the intratumoral and peritumoral regions of the lesions. Receiver-operating characteristic analysis was used to obtain the cut-off values for the parameters presenting a statistical difference between the two tumor groups. Furthermore, we investigated the potential effect of the region of interest (ROI) size on the quantification of diffusion properties in the intratumoral region of the lesions, by applying two different ROI methods. Results: Peritumoral N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, Cho/NAA and rCBV significantly differentiated glioblastomas from intracranial metastases. ADC and FA presented no significant difference between the two tumor groups. Conclusions: 1H-MRS and dynamic susceptibility measurements in the peritumoral regions may definitely aid in the differentiation of glioblastomas and solitary metastases. The quantification of the diffusion properties in the intratumoral region is independent of the ROI size placed.

Investigating brain tumor differentiation with diffusion and perfusion metrics at 3T MRI using pattern recognition techniques.

The aim of this study was to evaluate the contribution of diffusion and perfusion MR metrics in the discrimination of intracranial brain lesions at 3T MRI, and to investigate the potential diagnostic and predictive value that pattern recognition techniques may provide in tumor characterization using these metrics as classification features. Conventional MRI, diffusion weighted imaging (DWI), diffusion tensor imaging (DTI) and dynamic-susceptibility contrast imaging (DSCI) were performed on 115 patients with newly diagnosed intracranial tumors (low-and- high grade gliomas, meningiomas, solitary metastases). The Mann-Whitney U test was employed in order to identify statistical differences of the diffusion and perfusion parameters for different tumor comparisons in the intra-and peritumoral region. To assess the diagnostic contribution of these parameters, two different methods were used; the commonly used receiver operating characteristic (ROC) analysis and the more sophisticated SVM classification, and accuracy, sensitivity and specificity levels were obtained for both cases. The combination of all metrics provided the optimum diagnostic outcome. The highest predictive outcome was obtained using the SVM classification, although ROC analysis yielded high accuracies as well. It is evident that DWI/DTI and DSCI are useful techniques for tumor grading. Nevertheless, cellularity and vascularity are factors closely correlated in a non-linear way and thus difficult to evaluate and interpret through conventional methods of analysis. Hence, the combination of diffusion and perfusion metrics into a sophisticated classification scheme may provide the optimum diagnostic outcome. In conclusion, machine learning techniques may be used as an adjunctive diagnostic tool, which can be implemented into the clinical routine to optimize decision making.

Bone mineral density alterations in upper and lower extremities 12 months after stroke measured by peripheral quantitative computed tomography and DXA.

To evaluate the loss of trabecular and cortical bone mineral density (BMD) and geometric parameters of bone strength expressed by stress-strain index (SSI) in the proximal and distal forearm and the alterations of BMD in the hip of hemiplegic patient and 12 mo after stroke. Sixty-seven hemiplegic patients (43 men and 24 women) with a history of single completed strokes associated with unilateral weakness were enrolled in this prospective study. All patients underwent bone densitometry measurements at 3, 6, and 12 mo after the initial episode of stroke. Both paretic and normal forearms were examined by peripheral quantitative computed tomography (pQCT) at the 4% and 20% sites of the forearm length and both hips were examined by dual-energy X-ray absorptiometry (DXA) including the area of femoral neck and greater trochanter. The diagnosis of stroke was confirmed by cranial computed tomography. Motor function was assessed by the functional ambulation category (FAC) and spasticity by the modified Ashworth scale (MAS). We found statistically significant trabecular and cortical bone density reductions during the course of our study in the forearm, which was more profound on the paretic side. Trabecular bone loss and SSI measured at 4% of the paretic forearm in the male group represented a 12-mo decrease of 14.01% and 28.61%, respectively, and in the female group 9.29% and 19.17%, respectively. Cortical bone and SSI measured at the 20% site of paretic forearm in the male group corresponded to a 12-mo decrease of 4.02% and 7.43%, respectively, and in the female group 2.59% and 6.97%, respectively. Paretic femoral neck and trochanter measurements in males showed a reduction of 11.76% and 10.38%, respectively, and in females 13.04% and 12.6%, respectively. A significant loss of BMD and bone strength was found during the first year after stroke in both trabecular and cortical bone at the forearm and at the neck and great trochanter on the paretic hip. Most prominent BMD reduction was evident in men compared with perimenopausal women in the same age.

The role of diffusion and perfusion weighted imaging in the differential diagnosis of cerebral tumors: a review and future perspectives

The role of conventional Magnetic Resonance Imaging (MRI) in the detection of cerebral tumors has been well established. However its excellent soft tissue visualization and variety of imaging sequences are in many cases non-specific for the assessment of brain tumor grading. Hence, advanced MRI techniques, like Diffusion-Weighted Imaging (DWI), Diffusion Tensor Imaging (DTI) and Dynamic-Susceptibility Contrast Imaging (DSCI), which are based on different contrast principles, have been used in the clinical routine to improve diagnostic accuracy. The variety of quantitative information derived from these techniques provides significant structural and functional information in a cellular level, highlighting aspects of the underlying brain pathophysiology. The present work, reviews physical principles and recent results obtained using DWI/DTI and DSCI, in tumor characterization and grading of the most common cerebral neoplasms, and discusses how the available MR quantitative data can be utilized through advanced methods of analysis, in order to optimize clinical decision making.

Spontaneous spondylodiscitis: presentation, risk factors, diagnosis, management, and outcome.

BACKGROUND Spontaneous spondylodiscitis is an uncommon disease, which may result in serious complications with potentially high morbidity and mortality. We conducted a prospective case study over a 2-year period in order to analyze the clinical features, approaches to management, and outcome of spondylodiscitis. METHODS Eight consecutive patients (four men, four women; age range 53-82 years) suffering from spondylodiscitis were identified during the study period. Parameters recorded included: demographics, past medical history, predisposing factors, presenting signs and symptoms, spinal level and extension of the infection, laboratory indices of inflammation, microbiological testing, radiological assessment, kind and duration of treatment, follow-up magnetic resonance imaging (MRI) studies, and outcome. RESULTS Duration of symptoms varied from 14 to 90 days. All patients had back pain; fever>or=38 degrees C was present in 5/8 (62.5%) and neurological findings in 6/8 (75%). Diabetes mellitus was identified in six (75%). Most of the patients had elevated laboratory markers of inflammation. At the initial MRI, 12 anatomical levels were found. The microorganism was identified in 7/8 by blood or bone marrow cultures (50% Staphylococcus aureus). None of the patients underwent surgical intervention. Seven patients (87.5%) recovered to full activity; follow-up MRI study results were not always in parallel with the clinical improvement of patients. CONCLUSIONS Spontaneous spondylodiscitis should be considered in every patient with back pain accompanied by fever and laboratory markers of inflammation. The major predisposing risk factor seems to be uncontrolled diabetes. MRI appears to be the method of choice for confirming diagnosis. Timely and accurate diagnosis along with prompt administration of antibiotics appears mandatory for a favorable outcome and avoidance of surgical intervention.

The contribution of diffusion tensor imaging and magnetic resonance spectroscopy for the differentiation of breast lesions at 3T.

Background Conventional breast magnetic resonance imaging (MRI), including dynamic contrast-enhanced MR mammography (DCE-MRM), may lead to ambiguous diagnosis and unnecessary biopsies. Purpose To investigate the contribution of proton MR spectroscopy (1H-MRS) combined with diffusion tensor imaging (DTI) metrics in the discrimination between benign and malignant breast lesions. Material and Methods Fifty-one women with known breast abnormalities from conventional imaging were examined on a 3T MR scanner. DTI was performed during breast MRI, and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in the breast lesions and the contralateral normal breast. FA and ADC were compared between malignant lesions, benign lesions, and normal tissue. 1H-MRS was performed after gadolinium administration and choline peak was qualitatively evaluated. Results In our study 1H-MRS showed a sensitivity of 93.5%, specificity 80%, and accuracy 88.2%. FA was significantly higher in breast carcinomas compared to benign lesions. However, no significant difference was observed in ADC between benign and malignant lesions. The combination of Cho presence and FA achieved higher levels of accuracy and specificity in discriminating malignant from benign lesions over Cho presence or FA alone. Conclusion In conclusion, applying DTI and 1H-MRS together, adds incremental diagnostic value in the characterization of breast lesions and may sufficiently improve the low specificity of conventional breast MRI.

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.

High-resolution ultrasonography and 3.0 T magnetic resonance imaging in erosive and nodal hand osteoarthritis: high frequency of erosions in nodal osteoarthritis

Erosive osteoarthritis (EOA) is defined as hand osteoarthritis (OA) with interphalangeal joint erosions on plain radiographs. We sought to find ultrasound (US) and magnetic resonance imaging (MRI) features that could distinguish EOA from nodal hand OA (NOA). Symptomatic consecutive patients with hand OA as defined by the American College of Rheumatology criteria (13 EOA patients as defined by erosion in ≥1 interphalangeal joint and seven nodal OA patients) and five normal individuals were examined by plain radiography, US, and MRI. Patients and controls underwent evaluation of metacarpophalangeal and interphalangeal joints by US, and all fingers from second to fifth digit by MRI. A total of 240 joints in symptomatic patients were examined by both imaging modalities. Synovitis, osteophytes, cartilage loss, and erosions were frequently detected in the joints of patients with EOA and NOA. Six of seven patients with NOA had joint erosions that were seen on MRI or US scan but seen on plain radiographs. The overall concordance between MRI and US findings was substantial for osteophytes (κ = 0.79) and excellent for cysts (κ = 0.85), erosions (κ = 0.84), synovitis (κ = 0.82), and tenosynovitis (κ = 0.83) in both groups. Inflammatory changes, such as effusions and synovitis, and structural changes, such as erosions, were frequently detected by US and MRI in EOA and nodal OA. These findings may support the hypothesis that EOA could not be a separate entity but may represent the severe end of the spectrum of hand OA.

Long-term prognostic value of heart-rate recovery after treadmill testing in patients with diabetes mellitus

BACKGROUND Heart-rate recovery (HRR) is considered to be an independent predictor of cardiac and all-cause mortality. We examined the long-term prognostic value of HRR in patients suffering from diabetes mellitus. METHODS In this study, we included 258 consecutive patients. Patients whose HRR value or myocardial perfusion imaging could have been influenced by factors other than myocardial ischaemia, were excluded. The value of HRR was defined as the decrease in the heart-rate from peak exercise to 1 min after the termination of the exercise. All patients underwent SPECT myocardial perfusion imaging combined with exercise testing. Cardiovascular death and non-fatal myocardial infarction were considered as hard cardiac events, while late revascularization procedures as soft events. Cox proportional-hazard models were applied to evaluate the association between HRR and the investigated outcome. RESULTS During the follow-up period (30.8+/-6.9 months), hard cardiac events occurred in 21 (8%) patients (15 with abnormal HRR value, p<0.001), while 35 (14%) patients underwent revascularization (31 with abnormal HRR value, p<0.001). Considering it as a continuous variable, HRR was a strong predictor for both hard cardiac (coefficient=-0.41, SE=0.052, p<0.001) and soft cardiac events (coefficient=-0.63, SE=0.058, p<0.001). After adjustments were made for potential confounders, including scintigraphic variables, abnormal HRR remained an independent predictor for hard and soft cardiac events (p<0.001). CONCLUSION Our results suggest that among patients with diabetes, a decreased HRR is a significant independent predictor of hard and soft cardiac events.