Contrast-enhancing Brain Lesions Research Articles

Fluorescence Assisted Stereotactic Biopsy of Contrast-Enhancing Brain Lesions: Can YELLOW 560-nm Filter Substitute Frozen Section?

The factors on which the accuracy of stereotactic brain biopsy depends are the competence of the neurosurgeon in obtaining a representative sample and the ability of the neuro-pathologist to make a histological diagnosis from a minuscule sample. Over the years intraoperative frozen section has enhanced the diagnostic yield of this minimally invasive procedure. Use of fluorescence in achieving a greater extent of resection is well-established in contemporary neurosurgical practice. This ability of brain tumours to take up the fluorescein sodium dye and glow under the YELLOW 560nm filter has been utilized in a handful of studies to increase the diagnostic accuracy of stereotactic biopsy. We performed a prospective study where the fluorescein sodium dye was injected at a low dose and fluorescence of the biopsied core was compared with that of a tissue obtained from the normal parenchyma. Sample was labeled ‘truly fluorescent’ only when the glow was more than that of the tissue from normal parenchyma. On cross-tabulating the index test (true fluorescence status) and the reference standard test (final histopathological report) the sensitivity of acquiring a representative sample was found to be 94.74%, specificity was 100%. The positive predictive value (PPV) and negative predictive value (NPV) were calculated to be 100% and 50% respectively. The diagnostic yield was comparable to that of the intraoperative frozen section. The use of the YELLOW 560nm filter can make stereotactic biopsy faster, safer, less cumbersome, and more cost-effective, and can be used as a substitute for the frozen section in resource-constrained centers.

Normal Tissue Injury Induced by Photon and Proton Therapies: Gaps and Opportunities.

Despite technological advances in radiation therapy (RT) and cancer treatment, patients still experience adverse effects. Proton therapy (PT) has emerged as a valuable RT modality that can improve treatment outcomes. Normal tissue injury is an important determinant of the outcome; therefore, for this review, we analyzed 2 databases: (1) clinical trials registered with ClinicalTrials.gov and (2) the literature on PT in PubMed, which shows a steady increase in the number of publications. Most studies in PT registered with ClinicalTrials.gov with results available are nonrandomized early phase studies with a relatively small number of patients enrolled. From the larger database of nonrandomized trials, we listed adverse events in specific organs/sites among patients with cancer who are treated with photons and protons to identify critical issues. The present data demonstrate dosimetric advantages of PT with favorable toxicity profiles and form the basis for comparative randomized prospective trials. A comparative analysis of 3 recently completed randomized trials for normal tissue toxicities suggests that for early stage non-small cell lung cancer, no meaningful comparison could be made between stereotactic body RT and stereotactic body PT due to low accrual (NCT01511081). In addition, for locally advanced non-small cell lung cancer, a comparison of intensity modulated RTwith passive scattering PT (now largely replaced by spot-scanned intensity modulated PT), PT did not provide any benefit in normal tissue toxicity or locoregional failure over photon therapy. Finally, for locally advanced esophageal cancer, proton beam therapy provided a lower total toxicity burden but did not improve progression-free survival and quality of life (NCT01512589). The purpose of this review is to inform the limitations of current trials looking at protons and photons, considering that advances in technology, physics, and biology are a continuum, and to advocate for future trials geared toward accurate precision RT that need to be viewed as an iterative process in a defined path toward delivering optimal radiation treatment. A foundational understanding of the radiobiologic differences between protons and photons in tumor and normal tissue responses is fundamental to, and necessary for, determining the suitability of a given type of biologically optimized RT to a patient or cohort.

How can scanned proton beam treatment planning for low-grade glioma cope with increased distal RBE and locally increased radiosensitivity for late MR-detected brain lesions?

A novel risk model has recently been proposed for the occurrence of late contrast-enhancing brain lesions (CEBLs) after proton irradiation of low-grade glioma (LGG) patients. It predicts a strong dependence on dose-weighted linear-energy transfer (LETd effect) and an increased radiosensitivity of the ventricular proximity, a 4-mm fringe surrounding the ventricular system (VP4mm effect). On this basis, we investigated (A) how these two risk factors and patient-specific anatomical and treatment plan (TP) features contribute to normal tissue complication probability (NTCP) and (B) if conventional LETd -reduction techniques like multiple-field TP are able to reduce NTCP. (A) The LGG model cohort (N=110) was stratified with respect to prescribed dose, tumor grade, and treatment field configuration. NTCP predictions and CEBL occurrence rates per strata were analyzed. (B) The effect of multiple-field TP was investigated in two patient groups: (i) nine high-risk subjects with extended lateral target volumes who had developed CEBLs after single-beam treatments were retrospectively replanned with a clinical standard two-field setting using almost orthogonal fields and strictly opposing fields, (ii) single-field treatments were simulated for seven low-risk patients with small central target volumes clinically treated with two strictly opposing fields. (A) In the model cohort, we identified the exposure of the radiosensitive VP4mm fringe with proton field components of increased biological effectiveness as dominant NTCP driving factor. We observed that larger target volumes and location lateral to the main ventricles, both being characteristic for WHO°II tumors, presented with the highest complication risks. Among subjects of an equal dose prescription of 54Gy(RBE), the highest median NTCP was obtained for the WHO°II group treated with two fields using sharp angles. (B) Regarding the effect of multiple-field plans, we found that an NTCP reduction was only achievable in the low-risk group where the LETd effect dominates and the VP4mm effect is small. NTCP of the single-field plans was 23% higher compared to the clinical opposing field plan. In the high-risk group, where the VP4mm effect dominates the risk, both two-field scenarios yielded 44% higher NTCP predictions compared to the clinical single-field plans. The interplay of an increased radiosensitivity in the VP4mm fringe with proton field components of increased biological effectiveness creates a geometric complexity that can hardly be managed by current clinical TP. Our results underline that advanced biologically guided TP approaches become crucial for an effective risk minimization in proton therapy of LGG.

Clinical and demographic characteristics of primary progressive multiple sclerosis in Argentina: Argentinean registry cohort study (RelevarEM).

Primary progressive multiple sclerosis (PPMS) is an infrequent clinical form of multiple sclerosis (MS). Scarce information is available about PPMS in Latin America. The aim of this work is to describe the clinical and demographic characteristics of PPMS patients in Argentina. RelevarEM is a longitudinal, strictly observational registry in Argentina. Clinical and epidemiological data from PPMS patients were described. There were 144 cases of PPMS. They represented 7% of MS patients. The mean age was 44.1 years. The female:male ratio was 1.08. The mean Expanded Disability Status Scale (EDSS) score was 5.5 and the mean disease evolution time was 10.6 years. Oligoclonal bands were found in 72.9%. At the time of diagnosis, magnetic resonance imaging showed spinal cord lesions in 82.6% and contrast-enhancing brain lesions in 18.1% of patients. Almost one third of patients were treated with a disease-modifying drug, and ocrelizumab was the most frequently used (55.8%). PPMS is an infrequent subtype of MS and its recognition is of the highest importance as it has its own evolution, treatment, and prognosis. The importance of our research resides in providing local data and contributing to a better understanding of PPMS and its treatment in Latin America.

Late Contrast Enhancing Brain Lesions in Proton-Treated Patients With Low-Grade Glioma: Clinical Evidence for Increased Periventricular Sensitivity and Variable RBE

Late radiation-induced contrast-enhancing brain lesions (CEBLs) on magnetic resonance imaging (MRI) after proton therapy of brain tumors have been observed to occur frequently in regions of high linear energy transfer (LET) and in proximity to the ventricular system. We analyzed 110 patients with low-grade glioma treated with proton therapy to determine whether the risk for CEBLs is increased in proximity to the ventricular system and if there is a relationship between relative biological effectiveness (RBE) and LET. We contoured CEBLs identified on follow-up T1-MRI scans and computed dose and dose-averaged LET (LETd) distributions for all patients using the Monte Carlo method. We then performed cross-validated voxel-level logistic regression to predict local risks for image change and to extract model parameters, such as the RBE. From the voxel-level model, we derived a model for patient-level risk prediction based on the treatment plan. Of 110 patients, 23 exhibited 1 or several CEBLs on follow-up MRI scans. The voxel-level logistic model has an accuracy as follows: area under the curve of 0.94 and Brier score of 2.6 × 10-5. Model predictions are a 3-fold increased risk in the 4 mm region around the ventricular system and an LETd-dependent RBE of, for example, 1.20 for LETd = 2 keV/μm and 1.50 for LETd = 5 keV/μm. The patient-level risk model has an accuracy as follows: area under the curve of 0.78 and Brier score of 0.13. Our findings present clinical evidence for an increased risk in ventricular proximity and for a proton RBE that increases significantly with increasing LET. We present a voxel-level model that accurately predicts the localization of late MRI contrast change and extrapolate a patient-level model that allows treatment plan-based risk prediction.

MLTI-17. DIFFERENTIATION OF RADIATION INJURY FROM RECURRENT BRAIN METASTASIS USING COMBINED FET PET/MRI RADIOMICS

BACKGROUND: The aim of this study was to investigate the potential of combined radiomics textural feature analysis of contrast-enhanced MRI (CE MRI) and static O-(2-[18F]fluoroethyl)-L-tyrosine(FET) PET for the differentiation of recurrent brain metastasis from radiation injury. PATIENTS AND METHODS: Fifty-two patients with newly diagnosed or progressive contrast-enhancing brain lesions on MRI after radiotherapy (predominantly radiosurgery, 84% of patients) of brain metastases were additionally investigated using FET PET. Based on histology (n=19) or clinicoradiological follow-up (n=33), local recurrent brain metastases were diagnosed in 21 patients (40%) and radiation injury in 31 patients (60%). Forty-two features (shape-based, first and second order features) were calculated on both unfiltered and filtered CE MRI and summed FET PET images (20–40 min p.i). After feature selection, logistic regression models using a maximum of five features to avoid overfitting were calculated for each imaging modality separately and for the combined FET PET/MRI features. The resulting models were validated using cross-validation. Diagnostic accuracies were calculated for each imaging modality separately as well as for the combined model. RESULTS: For differentiation between radiation injury and brain metastasis recurrence, textural features extracted from CE MRI had a diagnostic accuracy of 81%. FET PET textural features revealed a slightly higher diagnostic accuracy of 83%. However, the highest diagnostic accuracy was obtained when combining CE MRI and FET PET features (accuracy, 89%). CONCLUSION: Our findings suggest that combined FET PET/MRI radiomics using textural feature analysis offers a great potential to contribute significantly to the management of patients with brain metastases. SUPPORT: This work was supported by the Wilhelm-Sander Stiftung, Germany

Glioneuronal brainstem tumor – It’s all in the eyes

A previously well man presented with several months’ history of neurological symptoms including diplopia and balance difficulties. Examination revealed fluctuating neurological deficits, fatigable weakness and slowed saccades. Extensive testing revealed mildly elevated cerebrospinal fluid protein, strongly positive single fiber electromyography and a dorsal pontine lesion at the floor of the 4th ventricle. An autoimmune process was felt to best account for the myasthenic presentation while the differential diagnoses for the brainstem lesion included glioma. Aggressive immunotherapy failed to halt clinical deterioration; over months he developed generalized weakness, aspiration pneumonia and died. Post-mortem analysis revealed glioneuronal tumor infiltration throughout the brainstem, cerebellum and along the meningeal surface. This is an unusual case of an infiltrative brainstem lesion, with the presentation suggesting a primary diagnosis of myasthenia gravis. The progressive nature of the illness, despite aggressive immune therapy, together with slow saccades, underscored a more sinister process. Cerebral imaging should be performed in patients with fluctuating neurological symptoms, progressive deterioration, and ocular, bulbar, respiratory, or pyramidal pattern deficits, and differentials for contrast-enhancing brain lesions should include primary brain tumors. In such cases, biopsy must proceed if the disease is of relatively recent onset, to facilitate diagnosis and maximize treatment opportunities.

Combined FET PET/MRI radiomics differentiates radiation injury from recurrent brain metastasis.

BackgroundThe aim of this study was to investigate the potential of combined textural feature analysis of contrast-enhanced MRI (CE-MRI) and static O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the differentiation between local recurrent brain metastasis and radiation injury since CE-MRI often remains inconclusive.MethodsFifty-two patients with new or progressive contrast-enhancing brain lesions on MRI after radiotherapy (predominantly stereotactic radiosurgery) of brain metastases were additionally investigated using FET PET. Based on histology (n = 19) or clinicoradiological follow-up (n = 33), local recurrent brain metastases were diagnosed in 21 patients (40%) and radiation injury in 31 patients (60%). Forty-two textural features were calculated on both unfiltered and filtered CE-MRI and summed FET PET images (20–40 min p.i.), using the software LIFEx. After feature selection, logistic regression models using a maximum of five features to avoid overfitting were calculated for each imaging modality separately and for the combined FET PET/MRI features. The resulting models were validated using cross-validation. Diagnostic accuracies were calculated for each imaging modality separately as well as for the combined model.ResultsFor the differentiation between radiation injury and recurrence of brain metastasis, textural features extracted from CE-MRI had a diagnostic accuracy of 81% (sensitivity, 67%; specificity, 90%). FET PET textural features revealed a slightly higher diagnostic accuracy of 83% (sensitivity, 88%; specificity, 75%). However, the highest diagnostic accuracy was obtained when combining CE-MRI and FET PET features (accuracy, 89%; sensitivity, 85%; specificity, 96%).ConclusionsOur findings suggest that combined FET PET/CE-MRI radiomics using textural feature analysis offers a great potential to contribute significantly to the management of patients with brain metastases.

Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase 18F-FET PET accuracy without dynamic scans.

We investigated the potential of textural feature analysis of O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET to differentiate radiation injury from brain metastasis recurrence. Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic 18F-FET PET. Tumour-to-brain ratios (TBRs) of 18F-FET uptake and 62 textural parameters were determined on summed images 20-40min post-injection. Tracer uptake kinetics, i.e., time-to-peak (TTP) and patterns of time-activity curves (TAC) were evaluated on dynamic PET data from 0-50min post-injection. Diagnostic accuracy of investigated parameters and combinations thereof to discriminate between brain metastasis recurrence and radiation injury was compared. Diagnostic accuracy increased from 81% for TBRmean alone to 85% when combined with the textural parameter Coarseness or Short-zone emphasis. The accuracy of TBRmax alone was 83% and increased to 85% after combination with the textural parameters Coarseness, Short-zone emphasis, or Correlation. Analysis of TACs resulted in an accuracy of 70% for kinetic pattern alone and increased to 83% when combined with TBRmax. Textural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic 18F-FET PET scans. • Textural feature analysis provides quantitative information about tumour heterogeneity • Textural features help improve discrimination between brain metastasis recurrence and radiation injury • Textural features might be helpful to further understand tumour heterogeneity • Analysis does not require a more time consuming dynamic PET acquisition.

Dynamic O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy.

The aim of this study was to investigate the potential of dynamic O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET for differentiating local recurrent brain metastasis from radiation injury after radiotherapy since contrast-enhanced MRI often remains inconclusive. Sixty-two patients (mean age, 55 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 76) on MRI after radiotherapy of brain metastases (predominantly stereotactic radiosurgery) were investigated with dynamic 18F-FET PET. Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) of 18F-FET uptake were determined (20-40 min postinjection) as well as tracer uptake kinetics (ie, time-to-peak and slope of time-activity curves). Diagnoses were confirmed histologically (34%; 26 lesions in 25 patients) or by clinical follow-up (66%; 50 lesions in 37 patients). Diagnostic accuracies of PET parameters for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or the chi-square test. TBRs were significantly higher in recurrent metastases (n = 36) than in radiation injuries (n = 40) (TBRmax 3.3 ± 1.0 vs 2.2 ± 0.4, P < .001; TBRmean 2.2 ± 0.4 vs 1.7 ± 0.3, P < .001). The highest accuracy (88%) for diagnosing local recurrent metastasis could be obtained with TBRs in combination with the slope of time-activity curves (P < .001). The results of this study confirm previous preliminary observations that the combined evaluation of the TBRs of 18F-FET uptake and the slope of time-activity curves can differentiate local brain metastasis recurrence from radiation-induced changes with high accuracy. 18F-FET PET may thus contribute significantly to the management of patients with brain metastases.

Glioma Recurrence Versus Radiation Necrosis: Single-Session Multiparametric Approach Using Simultaneous O-(2-18F-Fluoroethyl)-L-Tyrosine PET/MRI.

This study aimed to investigate the potential of hybrid gadolinium (Gd)-enhanced F-fluoroethyl-L-tyrosine (F-FET) PET/MRI in distinguishing recurrence from radiation necrosis using simultaneously acquired multiple structural and functional parameters. Twenty-six patients (5 female and 21 male patients; mean ± SD age, 51.58 ± 15.97 years) with single or multiple contrast-enhancing brain lesions (n = 32) on MRI after surgery and radiation therapy were evaluated with simultaneously acquired Gd-enhanced F-FET PET/MRI. They were then followed up with resurgery and histopathological diagnosis (n = 9) and/or clinical/MRI- or PET/MRI-based imaging follow-up (n = 17). PET/MR images were analyzed using manually drawn regions of interest over areas of maximal contrast enhancement and/or FET uptake. Maximum target-to-background ratio (TBRmax), mean target-to-background ratio (TBRmean), and choline-to-creatine (Cho/Cr) ratios as well as normalized mean relative cerebral blood volume (rCBVmean) and mean apparent diffusion coefficient (ADCmean) were determined. The accuracy of each parameter individually and in various possible combinations for differentiating recurrence versus radiation necrosis was evaluated using 2-tailed independent samples Student t test, multivariate analysis of variance, and multivariate receiver operating characteristic analysis. Positive histopathological finding and long-term imaging/clinical follow-up suggestive of disease progression served as criterion standard. Of 26 patients, 19 were classified as recurrence, with 7 patients showing radiation necrosis. Individually, TBRmax, TBRmean, ADCmean, and Cho/Cr ratios as well as normalized rCBVmean was significant in differentiating recurrence from radiation necrosis, with an accuracy of 93.8% for TBRmax, 87.5% for TBRmean, 81.3% for ADCmean, 96.9% for Cho/Cr ratio, and 90.6% for normalized rCBVmean. The accuracy of both normalized rCBVmean and ADCmean was improved in combination with TBRmax or Cho/Cr ratio. However, TBRmax (or TBRmean) with Cho/Cr ratio yielded the highest accuracy, approaching up to 97%. Furthermore, maximum area under the curve is achieved with the combination of TBRmean, CBV, and Cho/Cr values. Our findings suggest that FET uptake with Cho/Cr ratio and normalized rCBVmean could be most useful to distinguish primary glioma recurrence from radiation necrosis. Hybrid simultaneous multiparametric F-FET PET/MRI might play a significant role in the evaluation of patients with suspected glioma recurrence.

O7.05 * DIFFERENTIATION OF LOCAL RECURRENT BRAIN METASTASIS FROM RADIATION-INDUCED CHANGES USING O-(2-[18F]FLUOROETHYL)-L-TYROSINE PET

BACKGROUND: The aim of this study was to investigate the potential of O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET for differentiating local recurrent brain metastasis from radiation-induced changes after radiation therapy since the use of contrast-enhanced MRI for this issue is often difficult. METHODS: 38 patients (mean age, 54 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 49) on MRI after radiation therapy of brain metastases were investigated with dynamic 18F-FET PET. Maximum and mean tumor/brain ratios (20-40 min postinjection) (TBRmax, TBRmean) of 18F-FET uptake were determined. Time activity curves (TAC) were generated and the time-to-peak (TTP) was calculated. Furthermore, TACs of each lesion were assigned to one of the following curve patterns: (I) constantly increasing 18F-FET uptake; (II) 18F-FET uptake peaking early (TTP ≤ 20 min) followed by a plateau; and (III) 18F-FET uptake peaking early (TTP ≤ 20 min) followed by a constant descent. The diagnostic accuracy of the TBRmax and TBRmean of 18F-FET uptake and the curve patterns for the correct identification of recurrent brain metastasis was evaluated by receiver-operating-characteristic (ROC) analyses using subsequent histological analysis (17 lesions in 16 patients) or clinical course and MR imaging findings (32 lesions in 22 patients) as reference. RESULTS: Both TBRmax and TBRmean were significantly higher in patients with recurrent metastasis (n = 25) than in patients with radiation-induced changes (n = 24) (TBRmax 3.3 ± 1.0 vs. 2.3 ± 0.4, P < 0.001; TBRmean 2.2 ± 0.4 vs. 1.7 ± 0.1, P < 0.001). The sensitivity/specificity of 18F-FET PET for the correct identification of recurrent brain metastases was 84 / 79% using TBRmax (area under the curve, 0.851 ± 0.06, cut-off 2.6; P < 0.001), 92/83% using TBRmean (area under the curve, 0.901 ± 0.05, cut-off 1.9; P < 0.001), and 84/100% for curve patterns II and III vs. curve pattern I (P < 0.001). Highest sensitivity/specificity (96/88%) to diagnose local recurrent metastasis was obtained when both a TBRmean ≥1.9 and curve pattern II or III were present (area under the curve, 0.963 ± 0.03; P < 0.001). CONCLUSION: Our findings suggest that the combined evaluation of the TBRmean of 18F-FET uptake and the pattern of TAC can differentiate local brain metastasis recurrence from radiation-induced changes with high accuracy. 18F-FET PET may thus contribute significantly to the management of patients with brain metastases.

Role of O-(2-18F-Fluoroethyl)-l-Tyrosine PET for Differentiation of Local Recurrent Brain Metastasis from Radiation Necrosis

The aim of this study was to investigate the potential of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET for differentiating local recurrent brain metastasis from radiation necrosis after radiation therapy because the use of contrast-enhanced MRI for this issue is often difficult. Thirty-one patients (mean age ± SD, 53 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 40) on MRI after radiation therapy of brain metastases were investigated with dynamic (18)F-FET PET. Maximum and mean tumor-to-brain ratios (TBR(max) and TBR(mean), respectively; 20-40 min after injection) of (18)F-FET uptake were determined. Time-activity curves were generated, and the time to peak (TTP) was calculated. Furthermore, time-activity curves of each lesion were assigned to one of the following curve patterns: (I) constantly increasing (18)F-FET uptake, (II) (18)F-FET uptake peaking early (TTP ≤ 20 min) followed by a plateau, and (III) (18)F-FET uptake peaking early (TTP ≤ 20 min) followed by a constant descent. The diagnostic accuracy of the TBR(max) and TBR(mean) of (18)F-FET uptake and the curve patterns for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or Fisher exact test for 2 × 2 contingency tables using subsequent histologic analysis (11 lesions in 11 patients) or clinical course and MRI findings (29 lesions in 20 patients) as reference. Both TBR(max) and TBR(mean) were significantly higher in patients with recurrent metastasis (n = 19) than in patients with radiation necrosis (n = 21) (TBR(max), 3.2 ± 0.9 vs. 2.3 ± 0.5, P < 0.001; TBR(mean), 2.1 ± 0.4 vs. 1.8 ± 0.2, P < 0.001). The diagnostic accuracy of (18)F-FET PET for the correct identification of recurrent brain metastases reached 78% using TBR(max) (area under the ROC curve [AUC], 0.822 ± 0.07; sensitivity, 79%; specificity, 76%; cutoff, 2.55; P = 0.001), 83% using TBR(mean) (AUC, 0.851 ± 0.07; sensitivity, 74%; specificity, 90%; cutoff, 1.95; P < 0.001), and 92% for curve patterns II and III versus curve pattern I (sensitivity, 84%; specificity, 100%; P < 0.0001). The highest accuracy (93%) to diagnose local recurrent metastasis was obtained when both a TBR(mean) greater than 1.9 and curve pattern II or III were present (AUC, 0.959 ± 0.03; sensitivity, 95%; specificity, 91%; P < 0.001). Our findings suggest that the combined evaluation of the TBR(mean) of (18)F-FET uptake and the pattern of the time-activity curve can differentiate local brain metastasis recurrence from radionecrosis with high accuracy. (18)F-FET PET may thus contribute significantly to the management of patients with brain metastases.

Cutoff Value of Choline Concentration Reliably Reveals High-Grade Brain Tumors among Other Contrast-Enhancing Brain Lesions

To evaluate whether there is a cutoff value for a metabolite concentration measured by 1 H MR spectroscopy (MRS), which can be used to differentiate malignant brain tumors (high-grade gliomas, primary CNS lymphomas [PCNSL] and metastases) from other contrast-enhancing lesions like low-grade gliomas and non-neoplastic lesions. 1 H MRS was performed in 252 consecutive patients with space-occupying brain lesions which were enhanced with application of a contrast agent. Concentrations of N-acetyl-aspartate, total creatine, choline containing metabolites (total choline, tCho), lipids, and lactate were evaluated from the contrast-enhancing part of the lesions and from the normal appearing brain tissue. Linear discriminant analysis was used to find the best predictor for malignant brain tumors. In addition, receiver operating characteristic analysis (ROC) was performed to determine a cutoff value for the best predictor in detecting malignant brain tumors with a specificity of >95%. All brain tumors and 20 out of 47 nonneoplastic lesions were examined histopathologically. The remaining 27 diagnoses were based on MR imaging, clinical findings, and follow-up. The final diagnosis was 134 high-grade gliomas (WHO grade III/IV), 36 metastases, 9 PCNSL, 8 low-grade gliomas (WHO grade I/II), 34 infections, 9 infarctions, 2 hematomas, and 2 vasculitides. 18 patients were excluded due to insufficient spectral quality. The tCho concentration was the best predictor to differentiate malignant brain tumors from enhancing low-grade gliomas or non-neoplastic lesions (F=26.6 [df: 25.833], p<0.0005). The ROC revealed that a cutoff tCho value, based on an increase of ≥40% compared to normal, yielded a specificity of 100% and a sensitivity of 89.4% to correctly diagnose a malignant brain tumor. 1 H MRS reliably differentiates malignant brain tumors from other contrast-enhancing brain lesions. At least a 40% increase of tCho compared to normal brain tissue indicates a malignant tumor (WHO grade III/IV gliomas, PCNSL, metastases) with >90% specificity and sensitivity.

Cutoff Value of Choline Concentration Reliably Reveals High-Grade Brain Tumors among Other Contrast-Enhancing Brain Lesions

Cutoff Value of Choline Concentration Reliably Reveals High-Grade Brain Tumors among Other Contrast-Enhancing Brain Lesions

Low Incidence of Asymptomatic Contrast-Enhancing Brain Lesions in Japanese Patients with Multiple Sclerosis

Background: The number of contrast-enhancing brain lesions is used as an endpoint in multiple sclerosis (MS) clinical trials. However, the incidence of asymptomatic contrast-enhancing brain lesions (AEBLs) in Japanese patients with MS has not been determined. Objective: To describe the number of AEBLs per scan in Japanese patients with relapsing-remitting MS (RRMS). Methods: We reviewed the medical records of 23 Japanese patients with RRMS who showed (1) a stable or improving condition for at least 30 days before a magnetic resonance imaging (MRI) examination and (2) at least one relapse in the preceding year or two relapses in the preceding 2 years. Results: The percentage of patients with AEBLs was 39.1% (9/23 patients) and the number of AEBLs per scan was 0.37. Conclusions: The results suggest that the disease activity shown by brain MRI was lower in Japanese patients with MS compared with that in Caucasian patients.

Occult celiac disease presenting as epilepsy and MRI changes that responded to gluten-free diet

Celiac disease (CD), an autoimmune disorder involving hypersensitivity to gluten, has been associated with many neurologic manifestations, most commonly ataxia and neuropathy.1–3 We report contrast-enhancing brain lesions and epilepsy in a patient with previously occult CD that responded to a gluten-free diet (GFD). A 30-year-old, previously healthy man presented with a 2-year history of headaches and refractory seizures with postictal right hemiparesis and aphasia. He also had a constant milder hemiparesis. A brain MRI revealed multiple contrast-enhancing lesions involving white and gray matter. Serologic testing was unrevealing. A brain biopsy showed inflammation with reactive gliosis but no microglial nodules. There was also endothelial proliferation, without vasculitis. Special stains for periodic acid-Schiff, Gomori methenamine silver, Steiner, herpes simplex virus 1 and 2, amoeba, and encephalitis panel were all negative, as were CSF cultures for viral, bacterial, and fungal organisms. Despite treatment with glucocorticoids and multiple antiepileptic drugs, his seizures persisted, and subsequent MRI over the following 10 months found the appearance and disappearance …

Brain Tumors: Full- and Half-Dose Contrast-enhanced MR Imaging at 3.0 T Compared with 1.5 T—Initial Experience

To prospectively and intraindividually compare the effect of magnetic resonance (MR) imaging at a higher magnetic field strength (3.0 T) on contrast-to-noise ratio (CNR) at different doses of a T1-shortening contrast agent in patients with contrast-enhancing brain lesions, with 1.5-T MR imaging as a reference standard. Institutional review board approval and informed consent were obtained for all patient and volunteer studies. Twelve patients (six women, six men; mean age, 58 years; range, 29-76 years) with 12 enhancing brain lesions (11 patients with primary brain tumors and one with a solitary cerebral metastasis) underwent contrast material-enhanced MR imaging three times, on three separate days: once at 1.5 T with a full dose of 0.10 mmol/kg gadopentetate dimeglumine, once at 3.0 T with a full dose, and once at 3.0 T with half that dose, 0.05 mmol/kg. The same contrast-enhanced T1-weighted spin-echo images (repetition time msec/echo time msec, 500/12; section thickness, 5 mm; matrix, 256 x 205) were obtained at both 3.0 T and 1.5 T after prior optimization of parameters at 3.0 T. The number and conspicuity of enhancing brain lesions were assessed with blinded clinical image reading. Signal-to-noise ratio and CNR were determined with region of interest analysis of enhancing lesions and normal contralateral white matter. For 3.0 T with half the standard dose and with the full dose, CNR of lesions was intraindividually compared with CNR at 1.5 T with the full dose by using the Wilcoxon matched-pairs signed rank test. At 3.0 T and full dose, CNR was 2.8-fold higher than that at 1.5 T and full dose (P < .001). At the same time, higher lesion conspicuity at clinical image reading was observed. With only half the standard dose, MR imaging at 3.0 T still yielded higher CNR (1.3-fold higher) than that with full dose at 1.5 T (P < .01). With the same amount of contrast agent, MR imaging at 3.0 T offered a significantly higher CNR of enhancing cerebral lesions, compared with that at 1.5 T; even with the dose reduced by half, CNR was still higher at 3.0 T.

Inflammatory reaction in progressive multifocal leukoencephalopathy: harmful or beneficial?

Progressive multifocal leukoencephalopathy (PML) occurs in patients with profound immunosuppression. Although lesions are usually devoid of lymphoplasmocytic infiltrates, inflammatory forms of PML have been described, in both human immunodeficiency virus (HIV)-seropositive (HIV+) and -seronegative (HIV-) patients. In addition, PML has been shown to develop in HIV+ patients shortly after introduction of highly active antiretroviral therapy (HAART), despite a recovery of the immune system. Therefore, one could postulate that PML might arise in the context of an immune reconstitution syndrome. To examine the clinical and neuroradiological characteristics of inflammatory forms of PML, the authors performed a retrospective analysis of the patients seen at their institution since 1996 as well as a review of the literature. Of 39 HIV+ and HIV- PML patients, 5 (13%) presented with an inflammatory form of this disease. Two HIV+ patients developed PML soon after the onset of HAART, concomitant to immune recovery, as demonstrated by a decrease of HIV viral load (VL) and an increase of CD4+ T-cell count. Three patients (2 HIV+ and 1 HIV-) had signs of inflammation in the central nervous system (CNS) characterized by contrast-enhancing lesions on neuroimaging studies, and/or inflammatory infiltrates on brain biopsy. The presence of JC virus-specific cytotoxic T lymphocytes was demonstrated in 4/4 patients tested and the outcome was favorable in 3 of them. In agreement with previously published case reports, the data indicate that inflammatory reactions in PML are not infrequent, and that they are generally associated with a favorable prognosis. Therefore clinicians should not disregard the diagnosis of PML in presence of contrast-enhancing brain lesions, and should use caution before treating these immunosuppressed individuals with steroids.

Computerized tomography and magnetic resonance guided stereotactic brain biopsy in nonimmunocompromised and AIDS patients

The utility of stereotactic brain biopsy (SBB) in AIDS patients still remains controversial. The authors investigated SBB-related diagnostic accuracy, complications, and postoperative sequelae in nonimmunocompromised (NIC) patients and AIDS patients. The role of bioptic yield in treatment planning was also studied in AIDS patients. From 1990-95, 200 computerized tomography (CT) or magnetic resonance imaging (MRI)-guided SBBs were performed in our Department; 172 bioptic procedures were performed in NIC patients (169), and 28 SBBs in AIDS patients (27). The statistical significance was evaluated using the Fisher exact t-test. SBB accuracy was very high in both NIC (94.8%) and AIDS (92.9%) patients. Statistical analysis indicated nonsignificant (NS) differences between the two study groups (P > 0.05). Diagnostic yield resulted higher in contrast-enhancing (CE) brain lesions (98.6% in NIC and 95.0% in AIDS patients; P > 0.05; NS), than in non-CE lesions (74.1% in NIC and 87.5% in AIDS patients; P > 0.05; NS). The overall complication rate was similar in both groups (17.2% in NIC and 14.8% in AIDS patients, P > 0.05, NS). The most frequent complication was hemorrhage, with statistically negligible differences between the two study groups (P > 0.05). The frequency of complications involving minor/major morbidity or mortality was very low in NIC (5.9%, 0.6%, and 2.4%, respectively), and in AIDS (3.7%, 7.4%, and 0.0%, respectively) patients. Regarding the therapeutic impact of bioptic diagnosis for neuro-AIDS patients, the preoperative treatment attitude was modified in 23/27 cases (85.2%), and the empiric anti-toxoplasmosis regimen was changed or withdrawn in 17/21 patients (81.0%). Our experience demonstrated SBB to be an accurate, manageable, and reasonably safe diagnostic tool in both NIC and AIDS patients. These results suggest also that timely SBB indication in selected AIDS patients, reaching an early diagnosis, may on one side prevent unnecessary and potentially toxic empiric therapeutic regimens, and on the other address the appropriate treatment, thereby improving length and quality of life in such patients.