Martin Bulik

Potential of MR spectroscopy for assessment of glioma grading.

BACKGROUND Magnetic resonance spectroscopy (MRS) is an imaging diagnostic method based that allows non-invasive measurement of metabolites in tissues. There are a number of metabolites that can be identified by standard brain proton MRS but only a few of them has a clinical significance in diagnosis of gliomas including N-acetylaspartate, choline, creatine, myo-inositol, lactate, and lipids. METHODS In this review, we describe potential of MRS for grading of gliomas. RESULTS Low-grade gliomas are generally characterized by a relatively high concentration of N-acetylaspartate, low level of choline and absence of lactate and lipids. The increase in creatine concentration indicates low-grade gliomas with earlier progression and malignant transformation. Progression in grade of a glioma is reflected in the progressive decrease in the N-acetylaspartate and myo-inositol levels on the one hand and elevation in choline level up to grade III on the other. Malignant transformation of the glial tumors is also accompanied by the presence of lactate and lipids in MR spectra of grade III but mainly grade IV gliomas. It follows that MRS is a helpful method for detection of glioma regions with aggressive growth or upgrading due to favorable correlation of the choline and N-acetylaspartate levels with histopathological proliferation index Ki-67. Thus, magnetic resonance spectroscopy is also a suitable method for the targeting of brain biopsies. CONCLUSIONS Gliomas of each grade have some specific MRS features that can be used for improvement of the diagnostic value of conventional magnetic resonance imaging in non-invasive assessment of glioma grade.

The Diagnostic Ability of Follow-Up Imaging Biomarkers after Treatment of Glioblastoma in the Temozolomide Era: Implications from Proton MR Spectroscopy and Apparent Diffusion Coefficient Mapping.

Objective. To prospectively determine institutional cut-off values of apparent diffusion coefficients (ADCs) and concentration of tissue metabolites measured by MR spectroscopy (MRS) for early differentiation between glioblastoma (GBM) relapse and treatment-related changes after standard treatment. Materials and Methods. Twenty-four GBM patients who received gross total resection and standard adjuvant therapy underwent MRI examination focusing on the enhancing region suspected of tumor recurrence. ADC maps, concentrations of N-acetylaspartate, choline, creatine, lipids, and lactate, and metabolite ratios were determined. Final diagnosis as determined by biopsy or follow-up imaging was correlated to the results of advanced MRI findings. Results. Eighteen (75%) and 6 (25%) patients developed tumor recurrence and pseudoprogression, respectively. Mean time to radiographic progression from the end of chemoradiotherapy was 5.8 ± 5.6 months. Significant differences in ADC and MRS data were observed between those with progression and pseudoprogression. Recurrence was characterized by N-acetylaspartate ≤ 1.5 mM, choline/N-acetylaspartate ≥ 1.4 (sensitivity 100%, specificity 91.7%), N-acetylaspartate/creatine ≤ 0.7, and ADC ≤ 1300 × 10−6 mm2/s (sensitivity 100%, specificity 100%). Conclusion. Institutional validation of cut-off values obtained from advanced MRI methods is warranted not only for diagnosis of GBM recurrence, but also as enrollment criteria in salvage clinical trials and for reporting of outcomes of initial treatment.

Advanced MRI increases the diagnostic accuracy of recurrent glioblastoma: Single institution thresholds and validation of MR spectroscopy and diffusion weighted MR imaging

The accurate identification of glioblastoma progression remains an unmet clinical need. The aim of this prospective single-institutional study is to determine and validate thresholds for the main metabolite concentrations obtained by MR spectroscopy (MRS) and the values of the apparent diffusion coefficient (ADC) to enable distinguishing tumor recurrence from pseudoprogression. Thirty-nine patients after the standard treatment of a glioblastoma underwent advanced imaging by MRS and ADC at the time of suspected recurrence — median time to progression was 6.7 months. The highest significant sensitivity and specificity to call the glioblastoma recurrence was observed for the total choline (tCho) to total N-acetylaspartate (tNAA) concentration ratio with the threshold ≥ 1.3 (sensitivity 100.0% and specificity 94.7%). The ADCmean value higher than 1313 × 10− 6 mm2/s was associated with the pseudoprogression (sensitivity 98.3%, specificity 100.0%). The combination of MRS focused on the tCho/tNAA concentration ratio and the ADCmean value represents imaging methods applicable to early non-invasive differentiation between a glioblastoma recurrence and a pseudoprogression. However, the institutional definition and validation of thresholds for differential diagnostics is needed for the elimination of setup errors before implementation of these multimodal imaging techniques into clinical practice, as well as into clinical trials.

Post-WBRT cognitive impairment and hippocampal neuronal depletion measured by in vivo metabolic MR spectroscopy: Results of prospective investigational study

BACKGROUND AND PURPOSE The aim of this prospective study is to evaluate post-whole brain radiotherapy (WBRT) changes in hippocampal concentration of N-acetylaspartate (h-tNAA) as a marker of neuronal loss and to correlate those changes to neurocognitive function. MATERIAL AND METHODS Thirty-five patients with brain metastases underwent baseline single slice multi-voxel MR spectroscopy (MRS) examination for measurement of hippocampal h-tNAA together with baseline battery of neurocognitive tests focused on memory (Auditory Verbal Learning Test and Brief Visuospatial Memory Test - Revised) as well as quality of life questionnaires (EORTC QLQ-C30 a EORTC QLQ-BN20). Eighteen patients completed follow-up evaluation four months after standard WBRT (2 laterolateral fields, 10×3.0Gy, 6MV photons) and were included in this analysis. MRS and cognitive examinations were repeated and compared to baseline measurements. RESULTS Statistically significant decreases in h-tNAA were observed in the right (8.52-7.42mM; -12.9%, 95%CI: -7.6 to -16.4%) as well as in the left hippocampus (8.64-7.60mM; -12%, 95%CI: -7.9 to -16.2%). Statistically significant decline was observed in all AVLT and BVMT-R subtests with exception of AVLT_Recognition. Quality of life declined after WBRT (mean Δ -14.1±20.3 points in transformed 0-100 point scale; p=0.018) with no correlation to changes in hippocampal metabolite concentrations. Moderate positive correlation was observed between left h-tNAA concentration decrease and AVLT_TR decline (r=+0.32; p=0.24) as well as with AVLT_DR (r=+0.33; p=0.22) decline. Changes in right h-tNAA/Cr negatively correlated with AVLT_DR (r=-0.48; p=0.061). No correlation between right hippocampus h-tNAA and memory decline (AVLT) was observed. CONCLUSIONS Our results suggest hippocampal NAA concentrations decline after WBRT and MRS may be a useful biomarker for monitoring neuronal loss after radiotherapy.

Rare neurological presentation of human granulocytic anaplasmosis

Human granulocytic anaplasmosis (HGA) is a tick-borne, acute illness with increasing incidence [1]. It is caused by Anaplasma phagocytophilum proved to have a tick vector Ixodes ricinus in Europe. HGA is usually a mild or even asymptomatic illness with non-specific influenza-like symptoms, and is associated with variable but suggestive laboratory alterations. When comparing HGA with human ehrlichiosis caused by Ehrlichia chaffeensis, beside differences in geographical distribution, there is a close association with higher hospitalization rate (36% vs. 48.6%), morbidity and life-threatening complications (e.g. adult respiratory distress syndrome, disseminated intravascular coagulopathy, meningoencephalitis, renal failure) and mortality (0.6% vs. 1.9%) in E. chaffeensis cases [1]. A rush, as a clinical presentation, is also more frequently reported in patients with E. chaffeensis. HGA occurs in previously healthy individuals, and the disease severity is associated with the degree of compromised immunity of infected patients. The diagnosis is confirmed retrospectively using specific laboratory tests, which include positive polymerase chain reaction (PCR), identification of A. phagocytophilum in a culture of acute-phase blood, or the detection of specific antibodies to A. phagocytophilum in convalescent-phase serum samples. Doxycycline provides rapid and effective treatment.

P16.15DEVELOPING ROLE OF ADVANCED MRI TECHNIQUES FOR DIAGNOSIS OF HIGH-GRADE GLIOMA RELAPSE AFTER COMPLEX ONCOLOGY TREATMENT

PURPOSE/OBJECTIVES: High-grade gliomas (HGG) are the most common primary brain tumors of adults. Despite a multidisciplinary approach, HGGs frequently recur as a new gadolinium-enhanced MRI lesion at or near the site of the original tumor; thus, at the site of high-dose target volume for radiotherapy. An early differentiation between HGG relapse and changes in connection with oncology treatment (pseudoprogression or radionecrosis) is still problematic by commonly used diagnostic imaging techniques. The goal of our project is to verify whether a combination of diffusion-weighted MR imaging (DWI) and proton magnetic resonance spectroscopy (MRS) increase specificity of the conventional structural MRI with gadolinium for early non-invasive differentiation between of HGG relapse and pseudoprogression or radionecrosis. MATERIALS/METHODS: Patients (n= 26) with HGG and structural progression on MRI after neurosurgical resection and radiotherapy with concurrent administration of temozolomide underwent DWI expressed as ADC map and MRS focused on concentration of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lactate (Lac), and lipids (Lip). An etiology of the lesion was then established by a finding on a subsequent MRI or by a biopsy and correlated with results of the investigated MR techniques. RESULTS: Compared to the pseudoprogression or radionecrosis, the relapse of HGG was characterized by significantly lower ADC values, lower NAA concentration, appearance of Lac+Lip spectra, as well as by non-significant increase in Cho. We found very high sensitivity and specificity of ADC median value (≤1220 × 10−6 mm2/sec) and Cho/NAA ratio (≥1.7) to designate the MRI lesion with gadolinium uptake as the HGG relapse. CONCLUSION: It can be concluded that DWI (ADC value) and MRS (mainly Cho/NAA ratio) have the ability for early non-invasive differentiation of the HGG relapse from the pseudoprogression or radionecrosis after the oncology treatment. The project is supported by grants IGA MZC R NT/14120 and NT/14600 and the European Regional Development Fund Project FNUSA-IC RC (No. CZ.1.05/1.1.00/02.0123).

Utility of a rescue endovascular therapy for the treatment of major strokes refractory to full-dose intravenous thrombolysis.

OBJECTIVE Large artery occlusion (LAO) in patients with major stroke predicts poor revascularization by intravenous thrombolysis (IVT) and more likely results in a poor outcome. We focused on the effects of intra-arterial thrombolysis (IAT) and endovascular mechanical recanalization (EMR) as rescue therapies in major strokes refractory to IVT. METHODS A retrospective analysis of 87 patients (National Institutes of Health Stroke Scale >20), who did not respond to full-dose IVT due to LAO, was performed based on their endovascular therapy status. IAT was performed as an intraclot infusion of alteplase, and EMR was provided by the Solitaire device™ (Covidien, Dubin, Ireland). The recanalization and 3-month outcome rates after IAT/EMR were correlated with a group of patients who were scheduled to receive endovascular treatment but who underwent only IVT. RESULTS We achieved successful recanalization by IAT and EMR in 68.7% and 76.1% of patients, respectively. Despite no significant differences in mortality between IAT and EMR, a trend towards better outcomes after IAT and a statistically significant increase for outcome-modified Rankin scale (mRS) 0-3 (45.7%) and mRS 0-2 (34.9%) after EMR was noted when compared with IVT. The degree of recanalization did not correlate with the functional results except for the good-moderate outcome after successful recanalization by EMR. CONCLUSION EMR by the Solitaire device is a safe and beneficial method for the rescue treatment of patients with major stroke whose neurological status does not improve and who fail to recanalize the LAO after a 1-h full dose of IVT. ADVANCES IN KNOWLEDGE The article verifies efficiency of the Solitaire device in major strokes.