T2w Lesions Research Articles

Comparison of dynamic susceptibility contrast (DSC) using gadolinium and iron-based contrast agents in high-grade glioma at high-field MRI.

To compare DSC-MRI using Gadolinium (GBCA) and Ferumoxytol (FBCA) in high-grade glioma at 3T and 7T MRI field strengths. We hypothesized that using FBCA at 7T would enhance the performance of DSC, as measured by contrast-to-noise ratio (CNR). Ten patients (13 lesions) were assigned to 3T (6 patients, 6 lesions) or 7T (4 patients, 7 lesions). All lesions received 0.1mmol/kg of GBCA on day 1. Ten lesions (4 at 3T and 6 at 7T) received a lower dose (0.6mg/kg) of FBCA, followed by a higher dose (1.0-1.2mg/kg), while 3 lesions (2 at 3T and 1 at 7T) received only a higher dose on Day 2. CBV maps with leakage correction for GBCA but not for FBCA were generated. The CNR and normalized CBV (nCBV) were analyzed on enhancing and non-enhancing high T2W lesions. Regardless of FBCA dose, GBCA showed higher CNR than FBCA at 7T, which was significant for high-dose FBCA (p < .05). Comparable CNR between GBCA and high-dose FBCA was observed at 3T. There was a trend toward higher CNR for FBCA at 3T than 7T. GBCA also showed nCBV twice that of FBCA at both MRI field strengths with significance at 7T. GBCA demonstrated higher image conspicuity, as measured by CNR, than FBCA on 7T. The stronger T2* weighting realized with higher magnetic field strength, combined with FBCA, likely results in more signal loss rather than enhanced performance on DSC. However, at clinical 3T, both GBCA and FBCA, particularly a dosage of 1.0-1.2mg/kg (optimal for perfusion imaging), yielded comparable CNR.

Patient preparation for prostate MRI: A scoping review

PurposeTo perform a scoping review of the literature evaluating patient preparation for prostate MRI. MethodsWe conducted a search of English language literature, between 1989 and 2022 using MEDLINE and EMBASE for key terms: diet, enema, gel, catheter and anti-spasmodic agents linked to prostate MRI. Studies were reviewed for: level of evidence (LOE), study design and key results. Knowledge gaps were identified. ResultsThree studies evaluated dietary modification in 655 patients. LOE was 3. All studies showed improved DWI and T2W image quality (IQ) and reduced DWI artifact.Nine studies evaluated enema use in 1551 patients. Mean LOE was 2.8 (range 2–3). Six studies reported IQ; DWI and T2W IQ were significantly improved with enema in 5/6 and 4/6 studies respectively. Only one study evaluated DWI/T2W lesion visibility which was improved with enema. One study evaluated impact of enema on eventual prostate cancer diagnosis, showing no benefit in false negative reduction.One study (LOE = 2, 150 patients) evaluated rectal gel; however, in combination with enema showing improved DWI and T2W IQ, lesion visibility and PI-QUAL compared to no preparation.Two studies evaluated use of rectal catheter in 396 patients. LOE was 3. One study showed improved DWI and T2W IQ and artifact compared to no preparation; however, the other showed inferior results comparing rectal catheter to enema.Six studies evaluated anti-spasmodic agent use in 888 patients. Mean LOE was 2.8 (range 2–3). Benefit of anti-spasmodic agent use on image quality and artifact on DWI and T2W are conflicting with no clear benefit. ConclusionData evaluating patient preparation for prostate MRI is limited by level of evidence, study design and conflicting results. The majority of published studies do not evaluate impact of patient preparation on eventual prostate cancer diagnosis.

FAP-Specific Signalling Is an Independent Diagnostic Approach in ACC and Not a Surrogate Marker of MRI Sequences.

Simple SummaryFibroblast Activation Protein (FAP) is a new target for positron emission tomography and computed tomography (PET/CT) imaging of epithelial tumours, such as adenoid cystic carcinomas (ACCs). The current gold standard for ACC imaging is contrast enhanced (ce) MRI, where intertumoural heterogeneity leads to variable appearance on T1-weighted (T1w) and T2-weighted (T2w) images. The correlation of 68Gallium (68Ga)-labelled FAP-Inhibitor (FAPI) PET signals and MRI signals (contrast-enhanced T1w and T2w) of ACCs has not been described yet. Here, we analysed the correlation of 68Ga-FAPI PET signals and MRI signals of 12 ACC patients. 68Ga-FAPI PET signals showed a very weak positive correlation with ceT1w values (pooled correlation 0.114, 0.147 and 0.162 at 10, 60 and 180 min) and a weak negative correlation with T2w values. These results underline that 68Ga-FAPI PET signalling is not only a surrogate marker of MRI sequences but an independent signal in ACC patients.Background: Fibroblast Activation Protein (FAP) is a new target for positron emission tomography and computed tomography (PET/CT) imaging of epithelial tumours embedded in a fibrous stroma. Adenoid cystic carcinomas (ACCs) have shown elevated tracer uptake in 68Gallium (68Ga)-labelled FAPIs in previous studies. The current gold standard for ACC imaging is contrast-enhanced (ce) MRI, where intertumoural heterogeneity leads to variable appearance on T1-weighted (T1w) and T2-weighted (T2w) images. In this retrospective analysis, we correlated 68Ga-FAPI PET signalling at three time points with ceT1w and T2w MRI signals to further characterise the significance of 68Ga-FAPI uptake in ACCs. Methods: Clinical PET/CT scans of 12 ACC patients were performed at 10, 60 and 180 min post i.v. administration of 68Ga-labelled-FAPI tracer molecules. 68Ga-PET- and corresponding MRI-scans were co-registered, and 3D volumetric segmentations were performed on ceT1w and T2w lesions of co-registered MRI slides. Signal intensity values of 68Ga-FAPI PET signalling and ceT1w/T2w MRI scans were analysed for their pixelwise correlation in each patient. Pooled estimates of the correlation coefficients were calculated using the Fisher z-transformation. Results: 68Ga-FAPI PET signals showed a very weak positive correlation with ceT1w values (pooled correlation 0.114, 0.147 and 0.162 at 10, 60 and 180 min) and a weak negative correlation with T2w values (pooled correlation −0.148, −0.121 and −0.225 at 10, 60 and 180 min). Individual r-values at 60 min ranged from −0.130 to 0.434 in ceT1w and from −0.466 to 0.637 in T2w MRI scans. Conclusion: There are only slight correlations between the intensity of 68Ga-FAPI PET signals and tumour appearance in ceT1w or T2w MRI scans, which underlines that 68Ga-FAPI PET signalling is not a surrogate marker of MRI sequences but an independent signal.

Intrathecal IgM Synthesis Is Associated with Spinal Cord Manifestation and Neuronal Injury in Early MS.

ObjectiveIntrathecal Immunoglobulin M synthesis (IgMIntrathecal Fraction (IF) +) and spinal MRI lesions are both strong independent predictors of higher disease activity and severity in multiple sclerosis (MS). We investigated whether IgMIF + is associated with spinal cord manifestation and higher neuroaxonal damage in early MS.MethodsIn 122 patients with a first demyelinating event associations between (1) spinal versus (vs) non‐spinal clinical syndrome (2) spinal vs cerebral T2‐weighted (T2w) and (3) contrast‐enhancing (CE) lesion counts with IgGIF + (vs IgGIF −) or IgMIF + (vs IgMIF −) were investigated by logistic regression adjusted for age and sex, respectively. For serum neurofilament light chain (sNfL) analysis patients were categorized for presence or absence of oligoclonal IgG bands (OCGB), IgGIF and IgMIF (>0% vs 0%, respectively): (1) OCGB−/IgGIF −/IgMIF −; (2) OCGB+/IgGIF −/IgMIF −; (3) OCGB+/IgGIF +/IgMIF −; and (4) OCGB+/IgGIF +/IgMIF +. Associations between categories 2 to 4 vs category 1 with sNfL concentrations were analyzed by robust linear regression, adjusted for sex and MRI parameters.ResultsPatients with a spinal syndrome had a 8.36‐fold higher odds of IgMIF + (95%CI 3.03–23.03; p < 0.01). Each spinal T2w lesion (odds Ratio 1.39; 1.02–1.90; p = 0.037) and CE lesion (OR 2.73; 1.22–6.09; p = 0.014) was associated with an increased risk of IgMIF + (but not of IgGIF +); this was not the case for cerebral lesions. OCGB+/IgGIF +/IgMIF + category patients showed highest sNfL levels (estimate:1.80; 0.55–3.06; p < 0.01).InterpretationIntrathecal IgM synthesis is strongly associated with spinal manifestation and independently more pronounced neuroaxonal injury in early MS, suggesting a distinct clinical phenotype and pathophysiology. ANN NEUROL 2022;91:814–820

Intrathecal Immunoglobulin M Synthesis is an Independent Biomarker for Higher Disease Activity and Severity in Multiple Sclerosis.

ObjectiveWe aimed to determine in relapsing multiple sclerosis (MS) whether intrathecal synthesis of immunoglobulin (Ig) M and IgG is associated with outcomes reflecting inflammatory activity and chronic worsening.MethodsWe compared cerebrospinal fluid analysis, clinical and magnetic resonance imaging data, and serum neurofilament light chain (sNfL) levels at baseline and follow‐up in 530 patients with relapsing MS. Patients were categorized by the presence of oligoclonal IgG bands (OCGB) and intrathecal synthesis of IgG and IgM (intrathecal fraction [IF]: IgGIF and IgMIF). Relationships with the time to first relapse, sNfL concentrations, T2‐weighted (T2w) lesions, MS Severity Score (MSSS), and time to initiation of high‐efficacy therapy were analyzed in covariate‐adjusted statistical models.ResultsBy categorical analysis, in patients with IgMIF the median time to first relapse was 28 months shorter and MSSS on average higher by 1.11 steps compared with patients without intrathecal immunoglobulin synthesis. Moreover, patients with IgMIF had higher sNfL concentrations, more new/enlarging T2w lesions, and higher total T2w lesion counts (all p ≤ 0.01). These associations were absent or equally smaller in patients who were positive for only OCGB or OCGB/IgGIF. Furthermore, quantitative analyses revealed that in patients with IgMIF ≥ median, the time to first relapse and to initiation of high‐efficacy therapy was shorter by 32 and by 203 months, respectively (both p < 0.01), in comparison to patients with IgMIF < median. Dose‐dependent associations were also found for IgMIF but not for IgGIF with magnetic resonance imaging‐defined disease activity and sNfL.InterpretationThis large study supports the value of intrathecal IgM synthesis as an independent biomarker of disease activity and severity in relapsing MS. ANN NEUROL 2021;90:477–489

A preclinical study of diffusion-weighted MRI contrast as an early indicator of thermal ablation.

Intraoperative T2 -weighted (T2-w) imaging unreliably captures image contrast specific to thermal ablation after transcranial MR-guided focused ultrasound surgery, impeding dynamic imaging feedback. Using a porcine thalamotomy model, we test the unproven hypothesis that intraoperative DWI can improve dynamic feedback by detecting lesioning within 30 minutes of transcranial MR-guided focused ultrasound surgery. Twenty-five thermal lesions were formed in six porcine models using a clinical transcranial MR-guided focused ultrasound surgery system. A novel diffusion-weighted pulse sequence monitored the formation of T2-w and diffusion-weighted lesion contrast after ablation. Using postoperative T2-w contrast to indicate lesioning, apparent intraoperative image contrasts and diffusion coefficients at each lesion site were computed as a function of time after ablation, observed peak temperature, and observed thermal dose. Lesion sizes segmented from imaging and thermometry were compared. Image reviewers estimated the time to emergence of lesion contrast. Intraoperative image contrasts were analyzed using receiver operator curves. On average, the apparent diffusion coefficient at lesioned sites decreased within 5 minutes after ablation relative to control sites. In-plane lesion areas on intraoperative DWI varied from postoperative T2-w MRI and MR thermometry by mm2 and mm2 , respectively. The 0.25, 0.5, and 0.75 quantiles of the earliest times of observed T2-w and diffusion-weighted lesion contrast were 10.7, 21.0, and 27.8 minutes and 3.7, 8.6, and 11.8 minutes, respectively. The T2-w and diffusion-weighted contrasts and apparent diffusion coefficient values produced areas under the receiver operator curve of 0.66, 0.80, and 0.74, respectively. Intraoperative DWI can detect MR-guided focused ultrasound surgery lesion formation in the brain within several minutes after treatment.

Identification of Multiple Sclerosis lesion subtypes and their quantitative assessments with EDSS using neuroimaging

It would be helpful to have an automatic segmentation method to provide an acceptable performance of Magnetic Resonance Imaging (MRI) on Multiple Sclerosis (MS) subtypes that have important roles in cure procedure. This article presents a technique to classify MS lesion subtypes in MR images and then evaluates the correlation between lesion subtypes and Expanded Disability Status Scale (EDSS). The technique used textural features based on the Gray Level Co-occurrence Matrix (GLCM) and histogram information (mean and variance) to describe each lesion and normal tissue of FLAIR Images. Then it discriminated them with Support Vector Machine (SVM). A comprehensive post-processing module improved the quality of segmentation. We found corresponding areas in T2-weighted (T2-w), T1-weighted (T1-w) called black holes, and T1-weighted enhancing (T1-enhancing) by mapping the extracted lesions of FLAIR slices on them. Multi-Layer Perceptron (MLP) classified the mapped lesions in three classes of T2, black holes and T1-enhancing. Finally, the correlation between lesions volume of each class and EDSS was calculated. The performance evaluation resulted that the presented method allowed a higher value of sensitivity (86.1%) in black holes MS lesion subtypes classification. This sensitivity was higher than that obtained by others. This improvement beside the high accuracy (85.02%) and specificity (85.4%) make this pipeline an interest for clinical applications as an extra helpful way near neurologist for diagnosis. There were meaningful correlations between T2-w lesions volume and EDSS (R = 0.71, p = 0.03) and between black holes lesions and EDSS (R = 0.82, p = 0.004).

A fully convolutional neural network for new T2-w lesion detection in multiple sclerosis.

Longitudinal magnetic resonance imaging (MRI) has an important role in multiple sclerosis (MS) diagnosis and follow-up. Specifically, the presence of new T2-w lesions on brain MR scans is considered a predictive biomarker for the disease. In this study, we propose a fully convolutional neural network (FCNN) to detect new T2-w lesions in longitudinal brain MR images. One year apart, multichannel brain MR scans (T1-w, T2-w, PD-w, and FLAIR) were obtained for 60 patients, 36 of them with new T2-w lesions. Modalities from both temporal points were preprocessed and linearly coregistered. Afterwards, an FCNN, whose inputs were from the baseline and follow-up images, was trained to detect new MS lesions. The first part of the network consisted of U-Net blocks that learned the deformation fields (DFs) and nonlinearly registered the baseline image to the follow-up image for each input modality. The learned DFs together with the baseline and follow-up images were then fed to the second part, another U-Net that performed the final detection and segmentation of new T2-w lesions. The model was trained end-to-end, simultaneously learning both the DFs and the new T2-w lesions, using a combined loss function. We evaluated the performance of the model following a leave-one-out cross-validation scheme. In terms of the detection of new lesions, we obtained a mean Dice similarity coefficient of 0.83 with a true positive rate of 83.09% and a false positive detection rate of 9.36%. In terms of segmentation, we obtained a mean Dice similarity coefficient of 0.55. The performance of our model was significantly better compared to the state-of-the-art methods (p<0.05). Our proposal shows the benefits of combining a learning-based registration network with a segmentation network. Compared to other methods, the proposed model decreases the number of false positives. During testing, the proposed model operates faster than the other two state-of-the-art methods based on the DF obtained by Demons.

New and enlarging white matter lesions adjacent to the ventricle system and thalamic atrophy are independently associated with lateral ventricular enlargement in multiple sclerosis.

To investigate the association between new or enlarging T2-weighted (w) white matter (WM) lesions adjacent to the ventricle wall, deep grey matter (DGM) atrophy and lateral ventricular enlargement in multiple sclerosis (MS). Patients derived from the Genetic Multiple Sclerosis Associations study. Lateral ventricles and DGM were segmented fully automated at baseline and 5 years follow-up using Automatic Lateral Ventricle delineation (ALVIN) and Multiple Automatically Generated Templates brain segmentation algorithm (MAgeT), respectively. T2w and T1w lesions were manually segmented. To investigate the association between lesion distance to the ventricle wall and the lateral ventricle volume, we parcellated the WM into concentric periventricular bands using FMRIB Software Library. Associations between clinical and MRI parameters were assessed in generalized linear models using generalized estimating equations for repeated measures. We studied 127 MS patients. Lateral ventricles enlarged on average by 2.4%/year. Patients with new/enlarging T2w WM lesions between baseline and follow-up at 5 yearshad accelerated lateral ventricular enlargement compared with patients without (p = 0.004). This was true in a multivariable analysis adjusted for age, gender, and whole brain atrophy. When looking at the T2w lesions in different periventricular bands, we found the strongest association between new/enlarging T2w lesions and lateral ventricle enlargement for WM lesions adjacent to the ventricle system (p < 0.001). Moreover, and indepedent of new/enlarging WMlesions,DGM atrophy was associated with ventricular enlargement. In a multivariable analysis, this was driven by thalamic atrophy (p < 0.001). New/enlarging T2w lesions adjacent to the ventricle system and thalamic atrophy are independentlyassociated with lateral ventricular enlargement in MS.

Association of brain volume loss and long-term disability outcomes in patients with multiple sclerosis treated with teriflunomide

Background: Teriflunomide 14 mg significantly reduced brain volume loss (BVL) and confirmed disability worsening (CDW) compared with placebo in the TEMSO core study. Objective: To investigate the relationship between BVL from Baseline to Year 2 in the TEMSO core study and long-term CDW (Year 7) in the TEMSO long-term extension (NCT00803049). Methods: Structural Image Evaluation using Normalization of Atrophy determined BVL. Long-term CDW was assessed by Expanded Disability Status Scale confirmed for 12 and 24 weeks. An additional analysis evaluated the relative contribution of BVL (Year 2) and other outcomes as potential mediators of the effect of teriflunomide 14 mg on 12-week CDW. Results: Patients with the least BVL were significantly less likely to have 12- and 24-week CDW at Year 7 compared with patients with the most BVL. A mediation analysis revealed that BVL (Year 2) explained 51.3% of the treatment effect on CDW; new or enlarging T2w lesions over 2 years explained 30.8%, and relapses in the first 2 years explained 38.5%. Conclusions: These results highlight the potential predictive value of BVL earlier in the disease course on long-term disability outcomes. The mediation analysis suggests that teriflunomide may prevent disability worsening largely through its effects on BVL.

Clinical associations of T2-weighted lesion load and lesion location in small vessel disease: Insights from a large prospective cohort study

BackgroundSubcortical T2-weighted (T2w) lesions are very common in older adults and have been associated with dementia. However, little is known about the strategic lesion distribution and how lesion patterns relate to vascular risk factors and cognitive impairment. AimThe aim of this study was to analyze the association between T2w lesion load and location, vascular risk factors, and cognitive impairment in a large cohort of older adults. Methods1017 patients participating in a large prospective cohort study (INtervention project on cerebroVAscular disease and Dementia in the district of Ebersberg, INVADE II) were analyzed. Cerebral T2w white matter and deep grey matter lesions, the so-called white matter hyperintensities (WMHs), were outlined semi-automatically on fluid attenuated inversion recovery images and normalized to standard stereotaxic space (MNI152) by non-linear registration. Patients were assigned to either a low-risk or a high-risk group. The risk assessment considered ankle brachial index, intima media thickness, carotid artery stenosis, atrial fibrillation, previous cerebro-/cardiovascular events and peripheral artery disease as well as a score based on cholesterol levels, blood pressure and smoking. Separate lesion distributions were obtained for the two risk groups and compared using voxel-based lesion-symptom mapping. Moreover, we assessed the relation between lesion location and cognitive impairment (demographically adjusted z-scores of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery Plus, CERAD-NAB Plus) using voxel-based statistics (α = 0.05). ResultsA total of 878 out of 1017 subjects (86%) had evaluable MRI data and were included in the analyses (mean age: 68.2 ± 7.6 years, female: 515). Patients in the high-risk group were characterized by a significantly higher age, a higher proportion of men, a higher lesion load (p < 0.001), and a worse performance in some of the cognitive subdomain scores (p < 0.05). Voxels with significant associations to the subjects' cerebrovascular risk profiles were mainly found at locations of the corpus callosum, superior corona radiata, superior longitudinal fasciculus, internal and external capsule, and putamen. While several cognitive domains have shown significant associations with the participants’ total lesion burden (p < 0.05), no focal WMH locations were found to be associated with cognitive impairment. ConclusionAge, gender, several cognitive scores, and WMH lesion load were shown to be significantly associated with vascular risk factors in a population of older, but cognitively preserved adults. Vascular risk factors seem to promote lesion formation most severely at well-defined locations. While lesion load showed weak associations to some cognitive scores, no focal locations causing specific cognitive disturbances were identified in this large cohort of older adults.

A supervised framework with intensity subtraction and deformation field features for the detection of new T2-w lesions in multiple sclerosis.

IntroductionLongitudinal magnetic resonance imaging (MRI) analysis has an important role in multiple sclerosis diagnosis and follow-up. The presence of new T2-w lesions on brain MRI scans is considered a prognostic and predictive biomarker for the disease. In this study, we propose a supervised approach for detecting new T2-w lesions using features from image intensities, subtraction values, and deformation fields (DF).MethodsOne year apart multi-channel brain MRI scans were obtained for 60 patients, 36 of them with new T2-w lesions. Images from both temporal points were preprocessed and co-registered. Afterwards, they were registered using multi-resolution affine registration, allowing their subtraction. In particular, the DFs between both images were computed with the Demons non-rigid registration algorithm. Afterwards, a logistic regression model was trained with features from image intensities, subtraction values, and DF operators. We evaluated the performance of the model following a leave-one-out cross-validation scheme.ResultsIn terms of detection, we obtained a mean Dice similarity coefficient of 0.77 with a true-positive rate of 74.30% and a false-positive detection rate of 11.86%. In terms of segmentation, we obtained a mean Dice similarity coefficient of 0.56. The performance of our model was significantly higher than state-of-the-art methods.ConclusionsThe performance of the proposed method shows the benefits of using DF operators as features to train a supervised learning model. Compared to other methods, the proposed model decreases the number of false-positives while increasing the number of true-positives, which is relevant for clinical settings.

Using quantitative features extracted from T2-weighted MRI to improve breast MRI computer-aided diagnosis (CAD).

Computer-aided diagnosis (CAD) has been proposed for breast MRI as a tool to standardize evaluation, to automate time-consuming analysis, and to aid the diagnostic decision process by radiologists. T2w MRI findings are diagnostically complementary to T1w DCE-MRI findings in the breast and prior research showed that measuring the T2w intensity of a lesion relative to a tissue of reference improves diagnostic accuracy. The diagnostic value of this information in CAD has not been yet quantified. This study proposes an automatic method of assessing relative T2w lesion intensity without the need to select a reference region. We also evaluate the effect of adding this feature to other T2w and T1w image features in the predictive performance of a breast lesion classifier for differential diagnosis of benign and malignant lesions. An automated feature of relative T2w lesion intensity was developed using a quantitative regression model. The diagnostic performance of the proposed feature in addition to T2w texture was compared to the performance of a conventional breast MRI CAD system based on T1w DCE-MRI features alone. The added contribution of T2w features to more conventional T1w-based features was investigated using classification rules extracted from the lesion classifier. After institutional review board approval that waived informed consent, we identified 627 breast lesions (245 malignant, 382 benign) diagnosed after undergoing breast MRI at our institution between 2007 and 2014. An increase in diagnostic performance in terms of area under the curve (AUC) from the receiver operating characteristic (ROC) analysis was observed with the additional T2w features and the proposed quantitative feature of relative T2w lesion intensity. AUC increased from 0.80 to 0.83 and this difference was statistically significant (adjusted p-value = 0.020).

Klinische presentatie en diagnose met behulp van MRI van unilaterale hydrocefalus en een vermoeden van periventriculaire encefalitis bij een jonge hond

Een vier maanden oude Engelse buldog werd aangeboden met klachten van acute faciale spiertrekkingen, scheve kopstand en een abnormaal bewustzijn. Het neurologisch onderzoek was indicatief voor een multifocale hersenaandoening. Het hematologisch en biochemisch onderzoek was normaal. Magnetische resonantie van de hersenen onthulde een uitgesproken vergroting van de linker laterale ventrikel, met bijkomend een vergroting van het calvarium op dit niveau. Er waren ook periventriculaire letsels op T2W- en FLAIR-beelden zichtbaar met een matige contrastopname. Analyse van het cerebrospinale vocht toonde matig gemengde, mononucleaire pleiocytose en het testen op infectieziekten kwam negatief terug. De meest waarschijnlijke diagnose was unilaterale interne hydrocefalus veroorzaakt door periventriculaire encefalitis. Ondanks de slechte prognose werd de patiënt succesvol behandeld met prednisolone en fenobarbital. Dit is de eerste beschrijving van unilaterale hydrocefalus met vermoedelijke periventriculaire encefalitis bij een hond gediagnosticeerd met behulp van MRI.

Predicting long-term disability outcomes in patients with MS treated with teriflunomide in TEMSO.

Objective:To predict long-term disability outcomes in TEMSO core (NCT00134563) and extension (NCT00803049) studies in patients with relapsing forms of MS treated with teriflunomide.Methods:A post hoc analysis was conducted in a subgroup of patients who received teriflunomide in the core study, had MRI and clinical relapse assessments at months 12 (n = 552) and 18, and entered the extension. Patients were allocated risk scores for disability worsening (DW) after 1 year of teriflunomide treatment: 0 = low risk; 1 = intermediate risk; and 2–3 = high risk, based on the occurrence of relapses (0 to ≥2) and/or active (new and enlarging) T2-weighted (T2w) lesions (≤3 or >3) after the 1-year MRI. Patients in the intermediate-risk group were reclassified as responders or nonresponders (low or high risk) according to relapses and T2w lesions on the 18-month MRI. Long-term risk (7 years) of DW was assessed by Kaplan-Meier survival curves.Results:In patients with a score of 2–3, the risk of 12-week–confirmed DW over 7 years was significantly higher vs those with a score of 0 (hazard ratio [HR] = 1.96, p = 0.0044). Patients reclassified as high risk at month 18 (18.6%) had a significantly higher risk of DW vs those in the low-risk group (81.4%; HR = 1.92; p = 0.0004).Conclusions:Over 80% of patients receiving teriflunomide were classified as low risk (responders) and had a significantly lower risk of DW than those at increased risk (nonresponders) over 7 years of follow-up in TEMSO. Close monitoring of relapses and active T2w lesions after short-term teriflunomide treatment predicts a differential rate of subsequent DW long term.ClinicalTrials.gov identifier:TEMSO, NCT00134563; TEMSO extension, NCT00803049.

Epstein-Barr virus antibodies in serum and DNA load in saliva are not associated with radiological or clinical disease activity in patients with early multiple sclerosis.

ObjectiveTo investigate the association of Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) and viral capsid antigen (VCA) immunoglobulin (Ig)G antibodies in serum as well as EBV DNA load in saliva with radiological and clinical disease activity in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS).MethodsEBNA-1 and VCA immunoglobulin (Ig)G antibodies were determined in serum of 100 patients with CIS/early RRMS and 60 healthy controls. EBV DNA load was measured in saliva of 48 patients and 50 controls. Patients underwent clinical assessment with the Expanded Disability Status Scale (EDSS) and 3 Tesla magnetic resonance imaging at baseline and after a median of 20 months of follow-up (n = 63 for MRI, n = 71 for EDSS). The association of EBV parameters with occurrence of a second relapse, indicating conversion to clinically definite MS (CDMS), was evaluated over a median of 35 months of follow-up after the first clinical event (n = 89).ResultsEBNA-1 IgG antibody frequency (p = 0.00005) and EBNA-1 and VCA IgG antibody levels (p<0.0001 for both) were higher in patients than in controls. EBV DNA load in saliva did not differ between groups. Neither EBV antibody levels nor DNA load in saliva were associated with baseline or follow-up number or volume of T2-weighted (T2w) or contrast enhancing lesions, number of Barkhof criteria or the EDSS, or with the number of new T2w lesions, T2w lesion volume change or EDSS change on follow-up. Likewise, levels of EBV IgG antibodies in serum and DNA load in saliva were not associated with conversion to CDMS.ConclusionsWhile these findings confirm the association of EBV infection with early MS, neither EBNA-1 nor VCA IgG antibodies in serum nor EBV DNA load in saliva were associated with radiological or clinical disease activity in patients with CIS/early RRMS. These data are compatible with the concept that EBV may be a trigger for MS acting very early during the development of the disease.

A NOVEL METHOD FOR AUTOMATIC CLASSIFICATION OF MULTIPLE SCLEROSIS LESION SUBTYPES USING DIFFUSION TENSOR MR IMAGES

Purpose: An important work in making the treatment plan and following the therapeutic effects of multiple sclerosis (MS) patients is quantification of MS lesion subtypes. This study was designed to propose a new automatic method for classification of MS lesion subtypes based on conventional magnetic resonance (c-MR) and diffusion tensor MR (DT-MR) images. Method: In this paper, fuzzy [Formula: see text]-nearest neighbor (F-KNN) algorithm is used for classifying MS lesions into three subtypes including black holes (chronic), enhancing lesions (acute) and T2-lesions. In order to achieve this classification, F-KNN algorithm is used with features of c-MR images including T1-weighted (T1-w), fluid attenuated inversion recovery (FLAIR), gadolinium enhanced T1-weighted (Gad-E-T1-w) and T2-weighted (T2-w) and then with added features extracted from DT-MR images (diffusion indices) including mean diffusivity (MD) and fractional anisotropy (FA). Results: Evaluation of the proposed method was performed by manual classification of chronic, acute and T2-w lesions using the criterion of sensitivity (Se), specificity (Sp) and accuracy (Acc). The results showed that application of the c-MR with the DT-MR images makes possible the classification of MS lesion subtypes with high sensitivity and allows ability to evaluate MS disease in the treatment process.

Abstract 3271: Novel orthotopic pediatric high grade glioma xenografts evaluated with magnetic resonance imaging mimic human disease

Abstract Pediatric high grade gliomas (pHGG) may arise supratentorially in the cerebral hemispheres, or in midline structures such as the thalamus or the pons (diffuse intrinsic pontine glioma, DIPG). Tumors have distinct underlying biology compared with adult disease, with genetic subtypes corresponding to anatomical location. Differential mutations in genes encoding histone H3.3/H3.1 variants occur in supratentorial and midline tumors, while mutations in the gene encoding the BMP type I receptor ACVR1 are restricted to the pons and occur in a quarter of DIPGs. Co-option of existing brain vasculature in areas of infiltrative tumor growth leaves the blood brain barrier (BBB) intact. It is imperative to accurately model these tumors in vivo for the evaluation of emerging targeted therapeutics. Assessment of such models in situ is vital and requires sensitive functional imaging. T2-weighted (T2-w) MRI of orthotopically implanted PBT7 cells (supratentorial glioblastoma (GBM), 9yr old, H3F3A wt) showed heterogeneous tumors with relatively well defined borders. Hypointensity on T2-w and fluid-attenuated inversion recovery (FLAIR) images suggests the presence of necrosis and edema. Minimal heterogenous enhancement following Gd-DTPA administration demonstrated some loss of BBB integrity. FLAIR hyperintensity is used clinically to identify infiltrative tumor. Serially xenografted D-212 MG cells (supratentorial giant-cell GBM, 11yr old, H3F3A wt) formed tumors with FLAIR hyperintensity principally at the rim and Gd-DTPA enhancement prevalent at the tumor core. Histopathological assessment of H&amp;E staining confirmed the presence of masses with focal invasion at the periphery. Tumors established following pontine injection of HSJD-DIPG-007 cells (6yr old, H3F3A K27M, ACVR1 R206H) were identifiable by T2-w MRI hyperintensity in the pons and cerebellum. Histology confirmed a highly infiltrative tumor throughout the pons, cerebellum and leptomeninges, including the fissures of the cerebellum, which was validated by human nuclear antigen immunohistochemical staining. No extravasation of Gd-DTPA was observed indicating that the BBB remained intact. SU-DIPG-VI cells (6yr old, H3F3A K27M) grew diffusely in the pons with evidence of edema detected by T2-w MRI hyperintensity and FLAIR hypointensity. Diffusely hyperintense T2-w lesions with indistinct boundaries and limited Gd-DTPA extravasation were observed when imaging the diffusely infiltrative tumors resulting from thalamic implantation of QCTB-R059 primary thalamic GBM cells (10yr old, H3F3A K27M). In vivo propagation of primary and serially xenografted pHGG cells results in tumors that possess features of clinical disease, including infiltrative growth and necrosis. There is substantial potential for the use of these models to evaluate preclinical efficacy of novel therapeutics in a range of anatomical and biological subgroups of GBM and DIPG. Citation Format: Jessica K.R. Boult, Kathryn R. Taylor, Maria Vinci, Sergey Popov, Alexa Jury, Valeria Molinari, Marta M. Alonso, Wendy Ingram, Angel M. Caraboso, Michelle Monje, Suzanne A. Eccles, Chris Jones, Simon P. Robinson. Novel orthotopic pediatric high grade glioma xenografts evaluated with magnetic resonance imaging mimic human disease. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3271. doi:10.1158/1538-7445.AM2015-3271

Fahr's Disease: A Rare Neurological Disease

Abstract A 40-year-old unmarried female presented with abnormal involuntary choreo-athetoid movements involving both upper limbs for 5 years along with features, such as bouts of disorientation, anxiety, personality changes, reckless behaviour, inappropriate laughter and progressive decline in the neurological status. On neurological examination, her speech was dysarthric with mild choreiform movements involving both upper limbs. She had MMSE score of 20/30. MRI scans of the brain plain T1- and T2-weighted axial and flair coronal images were obtained. It showed calcifications as hyper-intense lesions on T1W and hypo-intense T2W lesions in bilateral basal ganglion and bilateral dentate nuclei of cerebellum, that is consistent with Fahr's syndrome.

Quantitative Measurement of tissue damage and recovery within new T2w lesions in pediatric- and adult-onset multiple sclerosis

Background: Children and adolescents with relapsing–remitting multiple sclerosis (RRMS) have a similar T2 lesion burden as adults matched for disease duration. However, it is unknown whether the degree of tissue destruction within lesions is also similar. Persistent reduced T1-weighted signal intensity within lesions indicates loss of tissue integrity. Objective: We aimed to compare change over a 2-year period in T1 intensity within new T2 lesions, from pre-lesion levels to chronic post-lesion levels, between pediatric and adult-onset MS. Methods: A two-point intensity-normalization method was used to generate normalized T1-weighted (NT1) images from T1-weighted data in 29 pediatric MS patients (age(mean±SD, years), disease duration (years)=15.7±2.4, 3.9±2.6) and 24 adult MS patients (36.7±8.9, 6.9±4.8). Subjects were imaged at three consecutive timepoints, 1 year apart. For each subject, a ‘new-T2’ lesion mask was created and the NT1 intensities ‘pre-lesion’, ‘peri-lesion’ and ‘post-lesion’ were determined. A longitudinal model was used to capture NT1 changes. Results: The NT1 in both groups failed to recover to pre-lesion values by 1 year post-lesion (p=0.0002), with children showing significantly better recovery than adults (p=0.0089). Conclusions: Both groups showed a significant chronic reduction of T1 intensity within new T2 lesions. However, children showed a significantly greater recovery of T1 intensity, suggesting that MS lesions in the pediatric MS population are less destructive, or that pediatric patients have greater reparative capacity.