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Brain metastases are common in patients with advanced melanoma and constitute a major cause of morbidity and mortality. Between 40% and 60% of melanomas harbor BRAF mutations. Selective BRAF inhibitor therapy has yielded improvement in clinical outcome; however, genetic discordance between the primary lesion and the metastatic tumor has been shown to occur. Currently, the only way to characterize the genetic landscape of a brain metastasis is by tissue sampling, which carries risks and potential complications. The aim of this study was to investigate the use of radiomics analysis for non-invasive identification of BRAF mutation in patients with melanoma brain metastases, based on conventional magnetic resonance imaging (MRI) data. We applied a machine-learning method, based on MRI radiomics features for noninvasive characterization of the BRAF status of brain metastases from melanoma (BMM) and applied it to BMM patients from two tertiary neuro-oncological centers. All patients underwent surgical resection for BMM, and their BRAF mutation status was determined as part of their oncological work-up. Their routine preoperative MRI study was used for radiomics-based analysis in which 195 features were extracted and classified according to their BRAF status via a support vector machine. The BRAF status of 53 study patients, with 54 brain metastases (25 positive, 29 negative for BRAF mutation) was predicted with mean accuracy = 0.79 ± 0.13, mean precision = 0.77 ± 0.14, mean sensitivity = 0.72 ± 0.20, mean specificity = 0.83 ± 0.11 and with a 0.78 area under the receiver operating characteristic curve for positive BRAF mutation prediction. Radiomics-based noninvasive genetic characterization is feasible and should be further verified using large prospective cohorts.

In recent years, several automatic methods have been proposed to differentiate between brain tumor recurrence and treatment-related changes following radiotherapy, based on conventional and advanced MRI methods. Vascular parameters extracted from dynamic contrast-enhanced (DCE) were suggested as potential markers for disease progression. Yet, most studies that proposed machine-learning methods or relayed on threshold values of DCE for classification, did not analyze separately Glioblastoma (GBM) and brain metastasis, and often offer the same method/threshold values, neglecting the different vascularity of these two tumor types. Understanding and quantifying the differences between tumors type can improve early diagnosis of recurrence and may improve the reliability of identifying treatment-related changes. The aim of this study was to quantify vascular parameters of tumor recurrence and to assess differences between GBM and brain metastasis, specifically metastasis of breast cancer. METHOD: 41 MRI scans were included: 24 from patients with GBM: 20 with recurrence and 4 with treatment-related changes, and 17 scans from patients with brain metastasis of breast cancer: 10 with recurrence and 7 with treatment-related changes (diagnosis were based on radiological follow-up/histopathology, when available). MRIs were performed on a 3.0 Tesla MRI scanner (Siemens MAGNETOM Prisma) and included T1, T1+contrast, and DCE images. DCE analysis was performed using DUSTER and Ktrans, Vp and Kep pharmacokinetic parameters were compared between groups. RESULTS: Patients with GBM often demonstrated both tumor recurrence and areas with treatment-related changes. Significantly differences were detected between tumor recurrence and treatment-related changes, and higher Vp and Ktrans were detected in recurrent GBM as compared to recurrent breast cancer metastasis. Cutoff for differentiation between tumor recurrence and treatment-related changes will be presented specifically for each tumor type. To conclude, when defining quantitative threshold values for clinical decision-making, the inherent differences between primary and metastatic brain tumors should be taken into account.

BACKGROUND Differentiation between glioblastoma and brain metastasis is highly important due to differing medical treatment strategies. While MRI is the modality of choice for the assessment of patients with brain tumors, differentiation between glioblastoma and solitary brain metastasis may be challenging due to their similar appearance on MRI. PURPOSE To differentiate between glioblastoma and brain metastasis subtypes using radiomics analysis based on conventional post-contrast T1 -weighted (T1 W) MRI. STUDY TYPE Retrospective. SUBJECTS Data were acquired from 439 patients: 212 patients with glioblastoma and 227 patients with brain metastasis (breast, lung, and others). FIELD STRENGTH/SEQUENCE Post-contrast 3D T1 W gradient echo images, acquired with 1.5 and 3.0 T MR systems. ASSESSMENT Analysis included image preprocessing, segmentation of tumor area, and features extraction including: patients' clinical information, tumor location, first- and second-order statistical, morphological, wavelet features, and bag-of-features. Following dimension reduction, classification was performed using various machine-learning algorithms including support-vector machine (SVM), k-nearest neighbor, decision trees, and ensemble classifiers. STATISTICAL TESTS For classification, the data were divided into training (80%) and testing datasets (20%). Following optimization of the classifiers, mean sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS For the testing dataset, the best results for differentiation of glioblastoma from brain metastasis were obtained using the SVM classifier with mean accuracy = 0.85, sensitivity = 0.86, specificity = 0.85, and AUC = 0.96. The best classification results between glioblastoma and brain metastasis subtypes were obtained using SVM classifier with mean accuracy = 0.85, 0.89, 0.75, 0.90; sensitivity = 1.00, 0.60, 0.57, 0.11; specificity = 0.76, 0.92, 0.87, 0.99; and AUC = 0.98, 0.81, 0.83, 0.57 for the glioblastoma, breast, lung, and other brain metastases, respectively. DATA CONCLUSION Differentiation between glioblastoma and brain metastasis showed a high success rate based on postcontrast T1 W MRI. Classification between glioblastoma and brain metastasis subtypes may require additional MR sequences with other tissue contrasts. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:519-528.

A novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus causing coronavirus disease 2019 (COVID-19) disease, which emerged as a global pandemic. Data regarding the implications of COVID-19 disease at early gestation on fetal and obstetric outcomes is scarce. Thus, our aim was to investigate the effect of first and second trimester maternal COVID-19 disease on fetal and perinatal outcomes. This was a prospective cohort study of pregnant women with a laboratory-proven SARS-COV-2 infection contracted prior to 26 weeks gestation. Women were followed at a single tertiary medical center by serial sonographic examinations every 4–6 weeks to assess fetal well-being, growth, placental function, anatomic evaluation and signs of fetal infection. Amniocentesis was offered to assess amniotic fluid SARS-COV-2-PCR (polymerase chain reaction) and fetal brain magnetic resonance imaging (MRI) was offered at 30–32 weeks gestation. Demographic, obstetric and neonatal data were collected from history intake, medical charts or by telephone survey. Perinatal outcomes were compared between women infected at first vs. second trimester. 55 women with documented COVID-19 disease at early gestation were included and followed at our center. The mean maternal age was 29.6 ± 6.2 years and the mean gestational age at viral infection was 14.2 ± 6.7 weeks with 28 (51%) women infected at the first trimester and 27 (49%) at the second trimester. All patients but one experienced asymptomatic to mild symptoms. Of 22 patients who underwent amniocentesis, none had evidence of vertical transmission. None of the fetuses exhibited signs of central nervous system (CNS) disease, growth restriction and placental dysfunction on serial ultrasound examinations and fetal MRI. Pregnancies resulted in perinatal survival of 100% to date with mean gestational age at delivery of 38.6 ± 3.0 weeks and preterm birth &lt, 37 weeks rate of 3.4%. The mean birthweight was 3260 ± 411 g with no cases of small for gestational age infants. The obstetric and neonatal outcomes were similar among first vs. second trimester infection groups. We conclude SARS-CoV-2 infection at early gestation was not associated with vertical transmission and resulted in favorable obstetric and neonatal outcomes.

To study the repeatability of plasma volume (vp) extracted from dynamic-contrast-enhanced (DCE) MRI in order to define threshold values for significant longitudinal changes, and to assess changes in patients with high-grade-glioma (HGG). Twenty eight healthy subjects, of which eleven scanned twice, were used to assess the repeatability of vp within the normal-appearing brain tissue and to define threshold values for significant changes based on least-detected-differences (LDD) of mean vp values and histogram comparisons using earth-mover’s-distance (EMD). Sixteen patients with HGG were scanned longitudinally with eight patients scanned before and following bevacizumab therapy. Longitudinal changes were assessed based on defined threshold values in comparison to RANO criteria. The threshold values for significant changes were: LDD = 0.0024 (ml/100 ml, 21%) for mean vp and EMD = 4.14. In patients, in 20/24 comparisons, no significant longitudinal changes were detected for vp within the normal-appearing brain tissue. Concurring results were obtained between changes in lesion volume (RANO criteria) and LDD or EMD values in cases diagnosed with progressive-disease, yet in about 50% of cases diagnosed with partial-response preliminary results demonstrated significant increase in vp despite significant reductions in lesion volume. In two patients, these changes preceded progression detected at follow-up scans. In general, a good concordance was obtained between LDD and EMD. This study shows high repeatability of vp and provides threshold values for significant changes in longitudinal assessment of patients with brain tumors. Preliminary results suggest the use of vp-DCE parameter to improve assessment of therapy response in patients with high-grade-glioma.

BACKGROUND High-grade gliomas (HGGs) induce both vasogenic edema and extensive infiltration of tumor cells, both of which present with similar appearance on conventional MRI. Using current radiological criteria, differentiation between these tumoral and nontumoral areas within the nonenhancing lesion area remains challenging. PURPOSE To use radiomics patch-based analysis, based on conventional MRI, for the classification of the nonenhancing lesion area in patients with HGG into tumoral and nontumoral components. STUDY TYPE Prospective. SUBJECTS In all, 179 MRI scans were obtained from 102 patients: 67 patients with HGG and 35 patients with brain metastases. A subgroup of 15 patients with HGG were scanned before and following administration of bevacizumab. FIELD STRENGTH/SEQUENCE Pre and postcontrast agent T1 -weighted-imaging (WI), T2 WI, FLAIR, diffusion-tensor-imaging (DTI), and dynamic-contrast-enhanced (DCE)-MRI at 3T. ASSESSMENT A total of 225 histograms and gray-level-co-occurrence matrix-based features were extracted from the nonenhancing lesion area. Tumoral volumes of interest (VOIs) were defined at the peritumoral area in patients with HGG; nontumoral VOIs were defined in patients with brain metastasis. Twenty machine-learning algorithms including support-vector-machine (SVM), k-nearest neighbor, decision-trees, and ensemble classifiers were tested. The best classifier was trained on the entire labeled data, and was used to classify the entire data. STATISTICAL TESTS Dimensional reduction was performed on the 225 features using principal component analysis. Classification results were evaluated based on the sensitivity, specificity, and accuracy of each of the 20 classifiers, first based on a training and testing dataset (80% of the labeled data) in a 5-fold manner, and next by applying the best classifier to the validation data (the remaining 20% of the labeled data). Results were additionally evaluated by assessing differences in dynamic-contrast-enhanced plasma-volume (vp ) and volume-transfer-constant (ktrans ) values between the two components using Mann-Whitney U-test/t-test. RESULTS The best classification into tumoral and nontumoral lesion components was obtained using a linear SVM classifier, with average accuracy of 87%, sensitivity 86%, and specificity of 89% (for the training and testing data). Significantly higher vp and ktrans values (P < 0.0001) were detected in the tumoral compared to the nontumoral component. Preliminary classification results in a subgroup of patients treated with bevacizumab demonstrated a reduction mainly in the nontumoral component following administration of bevacizumab, enabling early assessment of disease progression in some patients. DATA CONCLUSION A radiomics patch-based analysis enables classification of the nonenhancing lesion area in patients with HGG. Preliminary results were promising and the proposed method has the potential to assist in clinical decision-making and to improve therapy response assessment in patients with HGG. LEVEL OF EVIDENCE 1 Technical Efficacy Stage 4 J. Magn. Reson. Imaging 2018.

Contains fulltext : 181510.pdf (Publisher’s version ) (Open Access) Atypical brain development and early brain injury have profound and long lasting impact on the development, skill acquisition, and subsequent independence of a child. Heterogeneity is present at the brain level and at the motor level; particularly with respect to phenomena of bilateral activation and mirrored movements (MMs). In this multiple case study we consider the feasibility of using several modalities to explore the relationship between brain structure and/or activity and hand function: Electroencephalography (EEG), both structural and functional Magnetic Resonance Imaging (sMRI, fMRI), diffusion tensor imaging (DTI), transcranial magnetic stimulation (TMS), Electromyography (EMG) and hand function assessments. Methods : 15 children with unilateral CP (ages: 9.4±2.5 years) undertook hand function assessments and at least two additional neuroimaging and/or neurophysiological procedures: MRI/DTI/fMRI (n=13), TMS (n=11), and/or EEG/EMG (n=8). During the fMRI scans and EEG measurements, a motor task was performed to study cortical motor control activity during simple hand movements. DTI tractography analysis was used to study the corpus-callosum (CC) and cortico-spinal tracts (CST). TMS was used to study cortico-spinal connectivity pattern. Results: Type and range of severity of brain injury was evident across all levels of manual ability with the highest radiological scores corresponded to children poorer manual ability. Evidence of MMs was found in 7 children, mostly detected when moving the affected hand, and not necessarily corresponding to bilateral brain activation. When moving the affected hand, bilateral brain activation was seen in 6/11 children while 3/11 demonstrated unilateral activation in the contralateral hemisphere, and one child demonstrated motor activation predominantly in the supplementary motor area (SMA). TMS revealed three types of connectivity patterns from the cortex to the affected hand: a contralateral (n=3), an ipsilateral (n=4) and a mixed (n=1) connectivity pattern; again without clear association with MMs. No differences were found between children with and without MMs in lesion scores, motor fMRI laterality indices, CST diffusivity values, and upper limb function. In the genu, midbody, and splenium of the CC, higher fractional anisotropy values were found in children with MMs compared to children without MMs. The EEG data indicated a stronger mu-restoration above the contralateral hemisphere in 6/8 children and above the ipsilateral hemisphere in 2/8 children. Conclusion: The current results demonstrate benefits from the use of different modalities when studying upper-limb function in children with CP; not least to accommodate to the variations in tolerance and feasibility of implementation of the differing methods. These exposed multiple individual brain-reorganization patterns corresponding to different functional motor abilities. Additional research is warranted to understand the transactional influences of early brain injury, neuroplasticity and developmental and environmental factors on hand function in order to develop targeted interventions. 12 p.

Background: Accurate fetal brain volume estimation is of paramount importance in evaluating fetal development. The aim of this study was to develop an automatic method for fetal brain segmentation from magnetic resonance imaging (MRI) data, and to create for the first time a normal volumetric growth chart based on a large cohort. Subjects and Methods: A semi-automatic segmentation method based on Seeded Region Growing algorithm was developed and applied to MRI data of 199 typically developed fetuses between 18 and 37 weeks' gestation. The accuracy of the algorithm was tested against a sub-cohort of ground truth manual segmentations. A quadratic regression analysis was used to create normal growth charts. The sensitivity of the method to identify developmental disorders was demonstrated on 9 fetuses with intrauterine growth restriction (IUGR). Results: The developed method showed high correlation with manual segmentation (r2 = 0.9183, p < 0.001) as well as mean volume and volume overlap differences of 4.77 and 18.13%, respectively. New reference data on 199 normal fetuses were created, and all 9 IUGR fetuses were at or below the third percentile of the normal growth chart. Discussion: The proposed method is fast, accurate, reproducible, user independent, applicable with retrospective data, and is suggested for use in routine clinical practice.

Normal brain cells depend on glucose metabolism, yet they have the flexibility to switch to the usage of ketone bodies during caloric restriction. In contrast, tumor cells lack genomic and metabolic flexibility and are largely dependent on glucose. Ketogenic-diet (KD) was suggested as a therapeutic option for malignant brain cancer. This study aimed to detect metabolic brain changes in patients with malignant brain gliomas on KD using proton magnetic-resonance-spectroscopy (1H-MRS). Fifty MR scans were performed longitudinally in nine patients: four patients with recurrent glioblastoma (GB) treated with KD in addition to bevacizumab; one patient with gliomatosis-cerebri treated with KD only; and four patients with recurrent GB who did not receive KD. MR scans included conventional imaging and 1H-MRS acquired from normal appearing-white-matter (NAWM) and lesion. High adherence to KD was obtained only in two patients, based on high urine ketones; in these two patients ketone bodies, Acetone and Acetoacetate were detected in four MR spectra—three within the NAWM and one in the lesion area −4 and 25 months following initiation of the diet. No ketone-bodies were detected in the control group. In one patient with gliomatosis-cerebri, who adhered to the diet for 3 years and showed stable disease, an increase in glutamin + glutamate and reduction in N-Acetyl-Aspartate and myo-inositol were detected during KD. 1H-MRS was able to detect ketone-bodies in patients with brain tumors who adhered to KD. Yet it remains unclear whether accumulation of ketone bodies is due to increased brain uptake or decreased utilization of ketone bodies within the brain.

Introduction Understanding regarding the whole placental vascular network structure is limited. Our aim was to quantitatively characterize the human placental vascular tree ex-vivo using high-resolution MRI. Methods 34 normal placentas were rinsed and injected with a solution of gelatin and contrast agent through the umbilical vessels. A sample of six placentas taken from pregnancies with intrauterine-growth-restriction (IUGR) was used to demonstrate the potential application to cases with placental insufficiency. Structural ex-vivo MR scans of the placenta were performed using high resolution T1 weighted images. A semi-automatic method was developed to segment and characterize the placental vascular architecture: placental volume and cord insertion location; number of bifurcations, generations and vessels diameters. Results Different vascular patterns were found in placentas with central versus marginal cord-insertion. Based on the placental volume and number of bifurcations we were able to predict birth weight. Furthermore, preliminary results on IUGR sample demonstrated the potential of this method to differentiate between small newborns with suspected IUGR from small normal newborns who reached their full growth potential. Results obtained using the automatic method were validated against manual values demonstrating no significant differences or bias. Histopathology supported the imaging findings. Discussion: This is the first study to quantitatively characterize the human placental vascular architecture using high resolution ex-vivo MRI. Different patterns of vascular architecture may be related to different functioning of the placenta and affect fetal development. This method is simple, relatively fast, provides detailed information of the placental vascular architecture, and may have important clinical applications.

The interstitium-to-plasma rate constant (kep), extracted from dynamic contrast enhancement (DCE-MRI) MRI data, seems to have an important role in the assessment of patients with brain tumors. This parameter is affected by the slow behavior of the system, and thus is expected to be highly dependent on acquisition duration. The aim of this study was to optimize the scan duration and protocol of DCE-MRI for accurate estimation of the kep parameter in patients with high grade brain tumors. The effects of DCE-MRI scan duration and protocol design (continuous vs integrated scanning) on the estimated pharmacokinetic (PK) parameters and on model selection, were studied using both simulated and patient data. Scan duration varied, up to 60min for simulated data, and up to 25min in 25 MRI scans obtained from patients with high grade brain tumors, with continuous and integrated scanning protocols. Converging results were obtained from simulated and real data. Significant effect of scan duration was detected on kep. Scan duration of 9min, with integrated protocol in which the data are acquired continuously for 5min, and additional volumes at 7 and 9min, was sufficient for accurate estimation of even low kep values, with an average error of 3%. Over-estimation of the PK parameters was detected for scan duration 12min. An integrated protocol of 9min is suggested as optimal for clinical use in patients with high grade brain tumors. Lower acquisition time may result in over-estimation of kep when using ETM, and therefore care should be taken using model selection.

Knowledge regarding the association between functional connectivity and white-matter (WM) maturation of motor and visual networks in preterm infants at term equivalent age (TEA) and their association with behavioral outcome is currently limited. Thirty-two preterm infants born

To evaluate the interrelationship among impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort.The Tel Aviv Brain Acute Stroke Cohort study is a prospective cohort of mild-moderate ischemic stroke/TIA survivors without dementia who underwent a 3T MRI and were cognitively assessed at admission and for 24 months following stroke. Renal function was evaluated at admission by creatinine clearance (CCl) estimation. The volumes of ischemic lesions and preexisting white matter hyperintensities (WMH), brain atrophy, and microstructural changes of the normal-appearing white matter tissue were measured using previously validated methods.Baseline data were available for 431 participants. Participants with a CCl60 mL/min at baseline performed significantly worse in all cognitive tests over time (p = 0.001) than those with a CCl ≥60 mL/min and had larger WMH volume and cortical atrophy and smaller hippocampal volume (all p0.001). After 2 years, 15.5% of the participants were diagnosed with cognitive impairment. Multiple logistic regression analysis, controlling for traditional risk factors, suggested CCl60 mL/min at baseline as a significant predictor for the development of cognitive impairment 2 years after the index stroke (odds ratio 2.01 [95% confidence interval 1.03-3.92], p = 0.041).Impaired renal function is associated with increased WMH volume and cortical atrophy, known biomarkers of the aging brain, and is a predictor for cognitive decline 2 years after stroke/TIA. Decreased renal function may be associated with cerebral small vessel disease underlying poststroke cognitive decline, suggesting a new target for early intervention.

INTRODUCTION: Peripheral neurofibromas (NF) represent one of the most common clinical presentations of the NF1. About 10% of patients with NF1 develop malignant peripheral nerve-sheath tumours (MPNST), which is a major cause of morbidity in NF1 patients. Improved prognosis can be achieved if MPNST are diagnosed at an early stage permitting ablative surgery with wide resection margins. Better understanding regarding the natural history and biology of MPNST has been obtained in the last decade, however existing imaging modalities are still imperfect for diagnosis of MPNST. The aim of this study was to use a machine learning method in order to differentiate between benign plexiform neurofibromas from MPNST in patients with NF1 based on conventional MRI methods. METHODS: Among 23 NF1 patients with pathologically-defined MPNST treated in the last decade in TASMC, seven patients with available preoperative MRI studies were included in the study. For comparison, 7 patients with benign plexiform neurofibromas were chosen from the database of the Gilbert Israeli Neurofibromatosis Center. Regions of interest at tumor areas were extracted from the post contrast 2D T(1)-weighted spin-echo images acquired on 1.5/3T MRI systems. For each patient, speeded-up-robust (SURF) features were extracted from lesion areas using Matlab bagOfFeatures algorithm. The algorithm was trained with number of visual words =500, grid point selection method, strongest features=0.8 and grid step size (in pixels)=[5 5]. The algorithm was tested with 100 iterations, with the data being randomly split into training (80%) and testing (20%) datasets. RESULTS: A code-book of lesion representations was generated for each group and was given as input to the support-vector-machine (SVM) classifier. Classification results achieved mean accuracy=80%, mean sensitivity=72% and mean specificity=87%. CONCLUSION: Our preliminary results suggest that a quantitative image representation method based on Bag-of-Features may assist in the classification between benign plexiform neurofibromas and MPNST in NF1.

We report on a series of nine patients with high grade glioma (HGG) who developed punctate contrast-enhancing foci on MRI, several years after tumor treatment. The lesions were considered suspicious for tumor progression at their onset, but were proven over time to be benign in nature. Five of the patients were treated for glioblastoma; 3 for anaplastic astrocytoma, and one for anaplastic oligodendroglioma. Median age of the patients at diagnosis was 48 years (31–62 years). The mean time of onset of “suspicious spots” following treatment was 51 months after diagnosis (6–170 months). Of note, median overall survival of the group is 96 months; with none of the nine patients deceased, and only 2 patients known to have progression. The remainder of the 7 patients are free of active tumor and being followed off treatment. No apparent clinical manifestations of the lesions have been observed. The majority of the punctate lesions were of a dynamic nature; they appeared and spontaneously disappeared over time, without intervention. All lesions developed within the field of radiation treatment; some were contralateral to the tumor. Radiological characteristics of the lesions including analysis of SWI, DWI, and DCE magnetic resonance imaging sequences will be reported. Punctate enhancing foci in the region of radiation treatment are phenomena which may be manifestation of delayed treatment sequelae in HGG. Patients with these lesions are on average of younger age and have a particularly long survival. These lesions appeared several years following oncological treatment. The foci should be initially followed more closely until shown to be of a non-progressive nature; they should not be presumed to be indicative of tumor recurrence. Possible etiology of the lesions may be related to vascular changes induced by radiation.

Background Optic pathway gliomas (OPG) represent 5% of pediatric brain tumors and compose a major therapeutic dilemma to the treating physicians. While chemotherapy is widely used for these tumors, our ability to predict radiological response is still lacking. In this study, we use volumetric imaging to examine in detail the long-term effect of chemotherapy on the tumor as well as its various sub-components. Procedure The tumors of 15 patients with OPG, treated with chemotherapy, were longitudinally measured using our novel, previously described volumetric method. Patients were treated with up to five lines of chemotherapy. Sufficient follow-up imaging data, and patient's numbers, allowed for analysis of two treatment lines. Volumetric measurements of the tumors were segmented into solid-non-enhancing, solid-enhancing, and cystic components. Outcome analysis was done per specific treatment line and for the overall follow-up period. Results An average reduction of 9.7% (±23%) in the gross-total-solid volume (GTSV) was noted following treatment with vincristine and carboplatin. The cystic component grew under therapy by an average of 12.6% (±39%). When measured over the course of the whole study period, the cystic component grew by an average of 35% (±100%) and the GTSV increased by 12% (±35%). Conclusion Initial treatment with vincristine and carboplatin seems to have a minimal initial effect, mostly on the solid components. The cystic component in itself seems to be unaffected by chemotherapy, and contributes to the subsequent growth of the total volume. During the overall treatment period, both solid and cystic components grew regardless of combined treatment methods. Pediatr Blood Cancer 2015;62:1353–1359. © 2015 Wiley Periodicals, Inc.

Cerebral blood volume (CBV) is an important parameter for the assessment of brain tumors, usually obtained using dynamic susceptibility contrast (DSC) MRI. However, this method often suffers from low spatial resolution and high sensitivity to susceptibility artifacts and usually does not take into account the effect of tissue permeability. The plasma volume (v p) can also be extracted from dynamic contrast enhancement (DCE) MRI. The aim of this study was to investigate whether DCE can be used for the measurement of cerebral blood volume in place of DSC for the assessment of patients with brain tumors. Twenty-eight subjects (17 healthy subjects and 11 patients with glioblastoma) were scanned using DCE and DSC. v p and CBV values were measured and compared in different brain components in healthy subjects and in the tumor area in patients. Significant high correlations were detected between v p and CBV in healthy subjects in the different brain components; white matter, gray matter, and arteries, correlating with the known increased tissue vascularity, and within the tumor area in patients. This work proposes the use of DCE as an alternative method to DSC for the assessment of blood volume, given the advantages of its higher spatial resolution, its lower sensitivity to susceptibility artifacts, and its ability to provide additional information regarding tissue permeability.

BACKGROUND White matter hyperintensities (WMH) were shown to predict cognitive decline following stroke or transient ischemic attack (TIA). However, WMH are only one among other radiological markers of cerebral small vessel disease (SVD). OBJECTIVE The aim of this study was to determine whether adding other SVD markers to WMH improves prediction of post-stroke cognitive performances. METHODS Consecutive first-ever stroke or TIA patients (n = 266) from the Tel Aviv Acute Brain Stroke Cohort (TABASCO) study were enrolled. MRI scans were performed within seven days of stroke onset. We evaluated the relationship between cognitive performances one year following stroke, and previously suggested total SVD burden score including WMH, lacunes, cerebral microbleeds (CMB), and perivascular spaces (PVS). RESULTS Significant negative associations were found between WMH and cognition (p

This study proposes an automatic method for identification and quantification of different tissue components: the non-enhanced infiltrative tumor, vasogenic edema and enhanced tumor areas, at the subject level, in patients with glioblastoma (GB) based on dynamic contrast enhancement (DCE) and dynamic susceptibility contrast (DSC) MRI. Nineteen MR data sets, obtained from 12 patients with GB, were included. Seven patients were scanned before and 8 weeks following bevacizumab initiation. Segmentation of the tumor area was performed based on the temporal data of DCE and DSC at the group-level using k-means algorithm, and further at the subject-level using support vector machines algorithm. The obtained components were associated to different tissues types based on their temporal characteristics, calculated perfusion and permeability values and MR-spectroscopy. The method enabled the segmentation of the tumor area into the enhancing permeable component; the non-enhancing hypoperfused component, associated with vasogenic edema; and the non-enhancing hyperperfused component, associated with infiltrative tumor. Good agreement was obtained between the group-level, unsupervised and subject-level, supervised classification results, with significant correlation (r = 0.93, p < 0.001) and average symmetric root-mean-square surface distance of 2.5 ± 5.1 mm. Longitudinal changes in the volumes of the three components were assessed alongside therapy. Tumor area segmentation using DCE and DSC can be used to differentiate between vasogenic edema and infiltrative tumors in patients with GB, which is of major clinical importance in therapy response assessment.

Background: Patients with Parkinson’s disease have reduced gray matter volume and fractional anisotropy in both cortical and sub-cortical structures, yet changes in the pre-motor phase of the disease are unknown. Methods: A comprehensive imaging study using voxelbased morphometry and diffusion tensor imaging tract-based spatial statistics analysis was performed on 64 Ashkenazi Jewish asymptomatic first degree relatives of patients with Parkinson’s disease (30 mutation carriers), who carry the G2019S mutation in the leucine-rich repeat kinase 2 (LRRK2) gene. Results: No between-group differences in gray matter volume could be noted in either whole-brain or volume-of-interest analysis. Diffusion tensor imaging analysis did not identify group differences in white matter areas, and volume-of-interest analysis identified no differences in diffusivity parameters in Parkinson’s disease-related structures. Conclusions: G2019S carriers do not manifest changes in gray matter volume or diffusivity parameters in Parkinson’s disease-related structures prior to the appearance of motor symptoms. V C 2014 Interna

Purpose Stroke imaging studies during the acute phase are likely to precede several vascular brain mechanisms, which have an important role in patient outcome. The aim of this study was to identify within the lesion area during the subacute phase (≥1 day) reactive tissue, which may have the potential for recovery. Methods Twenty seven stroke patients from two cohorts were included. MRI performed during the subacute phase included conventional, perfusion and diffusion imaging. In cohort I, unsupervised multiparametric classification of the lesion area was performed. In cohort II threshold based classification was performed during the subacute phase, and radiological outcome was assessed at follow-up scan. Results Three tissue classes were identified in cohort I, referred to as irreversibly damaged, intermediary, and reactive tissue. Based on threshold values defined in cohort I, the reactive tissue was identified in 11/13 patients in cohort II, and showed tissue preservation/partial recovery in 9/11 patients at follow-up scan. The irreversibly damaged tissue was identified in 7/13 patients in cohort II, and predicted tissue necrosis in all cases. Conclusion Identification of reactive tissue following stroke during the subacute phase can improve radiological assessment, contribute to the understanding of brain recovery processes and has implications for new therapeutic approaches. Magn Reson Med 72:1381–1388, 2014. © 2013 Wiley Periodicals, Inc.

a b s t r a c t Background: Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas consid- ered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. Materials and methods: FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent- progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. Results: FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. Conclusion: This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice. © 2013 Published by Elsevier Ireland Ltd.

Current methods for evaluation of treatment response in glioblastoma are inaccurate, limited and time-consuming. This study aimed to develop a multi-modal MRI automatic classification method to improve accuracy and efficiency of treatment response assessment in patients with recurrent glioblastoma (GB).A modification of the k-Nearest-Neighbors (kNN) classification method was developed and applied to 59 longitudinal MR data sets of 13 patients with recurrent GB undergoing bevacizumab (anti-angiogenic) therapy. Changes in the enhancing tumor volume were assessed using the proposed method and compared with Macdonald's criteria and with manual volumetric measurements. The edema-like area was further subclassified into peri- and non-peri-tumoral edema, using both the kNN method and an unsupervised method, to monitor longitudinal changes.Automatic classification using the modified kNN method was applicable in all scans, even when the tumors were infiltrative with unclear borders. The enhancing tumor volume obtained using the automatic method was highly correlated with manual measurements (N=33, r=0.96, p0.0001), while standard radiographic assessment based on Macdonald's criteria matched manual delineation and automatic results in only 68% of cases. A graded pattern of tumor infiltration within the edema-like area was revealed by both automatic methods, showing high agreement. All classification results were confirmed by a senior neuro-radiologist and validated using MR spectroscopy.This study emphasizes the important role of automatic tools based on a multi-modal view of the tissue in monitoring therapy response in patients with high grade gliomas specifically under anti-angiogenic therapy.

The goal of the present study was to investigate whether spontaneous functional recovery following insult to the language-dominant hemisphere continues in the so-called “chronic stage,” and if so, to examine its neuro-functional correlates. We used a longitudinal functional magnetic resonance imaging (fMRI) block design, where each young patient served as his/her own control. Specifically, we examined whether language functions differed significantly in two monitoring sessions conducted years apart, both in the chronic stage, where almost no functional changes are expected. We focused on a unique cohort of young brain damaged patients with aphasiogenic lesions occurring after normal language acquisition, in order to maximize the potential of plasticity for language reorganization following brain damage. The most striking finding was that the linguistic recovery of our patients was significant not just relative to their linguistic scores on initial testing (T1), but also in absolute terms, relative to the respective age-matched normal population. Such improvement, therefore, cannot be simply attributed to the natural process of development. Overall, we found that right hemisphere (RH) activation was associated with better recovery in the chronic stage. Our longitudinal findings may challenge the view of recovery as ending within the first year following onset, suggesting that the RH may provide the substrate for ongoing plasticity in the damaged brain.

Our objective was to quantify and better understand white matter (WM) impairment in patients with amyotrophic lateral sclerosis (ALS) and to propose a model based on diffusion tensor imaging (DTI) for diagnosing patients with suspected ALS with upper motor neuron (UMN) signs. Twenty-six ALS patients (24 with prominent UMN signs and two with an isolated lower-motor neuron (LMN) syndrome) and 22 healthy volunteers were examined using DTI. Data analysis included voxel-based WM tract-based spatial statistics (TBSS), volume-of-interest analysis of the TBSS results and stream-line tractography analysis. Converging evidence revealed WM impairment along the corticospinal tracts and in the mid-body of the corpus callosum. This was demonstrated by reduced fractional anisotropy values caused by increased radial diffusivity, without significant changes in axial diffusivity. There were no significant correlations between diffusivity indices and patients' disability or disease duration. A discriminant analysis model based on the tractography results was designed to distinguish between patients with UMN signs and controls, yielding 87.5% sensitivity and 85% specificity. In conclusion, DTI can detect WM impairment in patients with ALS in several brain regions, and might be a sensitive tool for the diagnosis of ALS in the early stages of the disease with UMN involvement.

Optic pathway gliomas (OPGs) are diagnosed based on typical MR features and require careful monitoring with serial MRI. Reliable, serial radiological comparison of OPGs is a difficult task, where accuracy becomes very important for clinical decisions on treatment initiation and results. Current radiological methodology usually includes linear measurements that are limited in terms of precision and reproducibility.We present a method that enables semiautomated segmentation and internal classification of OPGs using a novel algorithm. Our method begins with co-registration of the different sequences of an MR study so that T1 and T2 slices are realigned. The follow-up studies are then re-sliced according to the baseline study. The baseline tumor is segmented, with internal components classified into solid non-enhancing, solid-enhancing, and cystic components, and the volume is calculated. Tumor demarcation is then transferred onto the next study and the process repeated. Numerical values are correlated with clinical data such as treatment and visual ability.We have retrospectively implemented our method on 24 MR studies of three OPG patients. Clinical case reviews are presented here. The volumetric results have been correlated with clinical data and their implications are also discussed.The heterogeneity of OPGs, the long course, and the young age of the patients are all driving the demand for more efficient and accurate means of tumor follow-up. This method may allow better understanding of the natural history of the tumor and provide a more advanced means of treatment evaluation.

The goal of this work was to study white matter maturation in young children with autism following previous reports of increased cerebral volume during early development, as well as arguments for abnormal neural growth patterns and regulation at this critical developmental period. We applied diffusion tensor imaging (DTI) and high b value diffusion-weighted imaging (DWI) to young children diagnosed with autism and to a typically developing (TD) control group. Fractional anisotropy (FA), probability and displacement were measured in overall analysis as well as in regions of interest (ROI). Individual data points of children with autism were compared to the developmental curves obtained from typically developing children. Increased restriction, reflected in significantly increased FA and probability along with reduced displacement values, was detected in overall analysis as well as in several brain regions. Increased restriction, suggesting an early and accelerated abnormal maturation of white matter, was more dominant in the left hemisphere and was mainly detected in the frontal lobe. No changes were detected in the occipital lobes. These results support previous claims of abnormal brain overgrowth in young children with autism and are in contrast to the decreased restricted diffusion reported in previous studies in adolescent with autism.

Alzheimer's disease (AD) and Vascular Dementia (VaD) are the most common types of dementia and are progressive diseases affecting millions of people. Despite the high sensitivity of MRI to neurological disorders it has not thus far been found to be specific for the detection of either of these pathologies. In the present study high b-value q-space diffusion-weighted MRI (DWI) was applied to VaD and AD. Controls (N=4), VaD patients (N=8) and AD patients (N=6) were scanned with high b-value DWI, which emphasizes the water component which exhibits restricted diffusion. VaD patients were found to present major WM loss while, in AD, the major pathology found was GM changes, as expected. Also, WM changes in VaD and AD were of a different pattern, more specific to frontal and temporal areas in AD and more widespread in VaD. This pattern of WM changes may be utilized as a diagnosis criterion. Conventional diffusion tensor imaging did not show significant changes between either of the groups and controls. These results demonstrate the potential of high b-value DWI in the diagnosis of dementia.

Background. Motor-learning interventions may improve hand function in children with unilateral cerebral palsy (UCP) but with inconsistent outcomes across participants. Objective. To examine if pre-intervention brain imaging predicts benefit from bimanual intervention. Method. Twenty children with UCP with Manual Ability Classification System levels I to III, aged 7-16 years, participated in an intensive bimanual intervention. Assessments included the Assisting Hand Assessment (AHA), Jebsen Taylor Test of Hand Function (JTTHF) and Children’s Hand Experience Questionnaire (CHEQ) at baseline (T1), completion (T2) and 8-10 weeks post-intervention (T3). Imaging at baseline included conventional structural (radiological score), functional (fMRI) and diffusion tensor imaging (DTI). Results. Improvements were seen across assessments; AHA ( P = 0.04), JTTHF ( P < .001) and CHEQ ( P < 0.001). Radiological score significantly correlated with improvement at T2; AHA ( r = .475) and CHEQ ( r = .632), but negatively with improvement on unimanual measures at T3 (JTTFH r = −.514). fMRI showed negative correlations between contralesional brain activation when moving the affected hand and AHA improvements (T2: r = −.562, T3: r = −0.479). Fractional Anisotropy in the affected posterior limb of the internal capsule correlated negatively with increased bimanual use on CHEQ at T2 ( r = −547) and AHA at T3 ( r = −.656). Conclusions. Children with greater structural, functional and connective brain damage showed enhanced responses to bimanual intervention. Baseline imaging may identify parameters predicting response to intervention in children with UCP.

Differentiation between treatment-related changes and progressive disease (PD) remains a major clinical challenge in the follow-up of patients with high grade brain tumors. The aim of this study was to differentiate between treatment-related changes and PD using dynamic contrast enhanced (DCE) MRI. Twenty patients were scanned using conventional, DCE-MRI and MR spectroscopy (total of 44 MR scans). The enhanced lesion area was extracted using independent components analysis of the DCE data. Pharmacokinetic parameters were estimated from the DCE data based on the Extended-Tofts-Model. Voxel based classification for treatment-related changes versus PD was performed in a patient-wise leave-one-out manner, using a support vector machine classifier. DCE parameters, K (trans), v e, k ep and v p, significantly differentiated between the tissue types. Classification results were validated using spectroscopy data showing significantly higher choline/creatine values in the extracted PD component compared to areas with treatment-related changes and normal appearing white matter, and high correlation between choline/creatine values and the percentage of the identified PD component within the lesion area (r = 0.77, p

Calcification is a rare phenomenon in high grade glioma (HGG). CT scans are sensitive to mineralization but used infrequently for tumor assessment in the MRI era. The presence of calcification can be overlooked on routine MRI. Calcification may reflect chronicity and natural changes in the tumor or its milieu over time and may be accelerated by certain treatments. Calcification may have clinical significance which could signal potential risk for stroke or hemorrhage related to particular therapies; or it may be a positive prognostic factor for treatment response. The true incidence and relevance of calcification in HGG and relation to therapy is unclear. During treatment of HGG patients with bevacizumab (BVZ) we observed significant tumor calcification on brain CT. We performed a retrospective review of HGG patients treated with BVZ to quantitate the incidence of calcification in this group compared to those treated with cytotoxic therapy alone. Sixty-two patients with progressive HGG were treated with BVZ and a cytotoxic agent. Among 19 patients treated for 6+ months, 12 had a CT scan performed. We observed an unexpected phenomenon of calcification in the CT scans of several patients. We were also able to comparatively quantitate the incidence of calcification in a control group of primary glioblastoma (GB) patients not exposed to BVZ therapy. The incidence of calcification in the general GB population is increased with longer survival. The phenomenon is increased with anti-angiogenic therapy for brain tumors. Calcification may have significance as a predictor for treatment response.

Neuroplasticity studies examining children with hemiparesis (CH) have focused predominantly on unilateral interventions. CH also have bimanual coordination impairments with bimanual interventions showing benefits. We explored neuroplasticity following hand-arm bimanual intensive therapy (HABIT) of 60 hours in twelve CH (6 females, mean age 11 ± 3.6 y). Serial behavioral evaluations and MR imaging including diffusion tensor (DTI) and functional (fMRI) imaging were performed before, immediately after, and at 6-week follow-up. Manual skills were assessed repeatedly with the Assisting Hand Assessment, Children’s Hand Experience Questionnaire, and Jebsen-Taylor Test of Hand Function. Beta values, indicating the level of activation, and lateralization index (LI), indicating the pattern of brain activation, were computed from fMRI. White matter integrity of major fibers was assessed using DTI. 11/12 children showed improvement after intervention in at least one measure, with 8/12 improving on two or more tests. Changes were retained in 6/8 children at follow-up. Beta activation in the affected hemisphere increased at follow-up, and LI increased both after intervention and at follow-up. Correlations between LI and motor function emerged after intervention. Increased white matter integrity was detected in the corpus callosum and corticospinal tract after intervention in about half of the participants. Results provide first evidence for neuroplasticity changes following bimanual intervention in CH. This project was funded by grants from Guy’s and St Thomas’ Charity, Marnie Kimelman Trust and ILAN, the Israeli Association for Disabled children. Beit Issie Shapiro funded and provided the camp venue. D. Green was supported by a grant from the Department of Immigration and Absorption during 2010-2011.

High b value diffusion weighted magnetic resonance imaging (high-b DWI) was used to characterize white matter changes in the brain of patients with vascular dementia (VaD). Hyperintense white matter areas detected by T2-weighted magnetic resonance imaging (MRI) represent lesions, also termed leukoaraiosis that are very common in VaD as well as in other types of dementia. Therefore, the role of white matter changes in the cognitive and memory decline that occurs in VaD patients is still under debate. High-b DWI, analyzed using the q-space approach, is a more sensitive MRI method for detection of white matter changes. High-b DWI revealed massive white matter loss in VaD patients that surpassed the boundaries of T2 hyperintensities. This technique, therefore, might serve as a better indication for the extensive nerve fiber loss in the white matter that is caused by vascular disease.

Identification of early changes in Dopamine-Transporter (DaT) SPECT imaging expected in the prodromal phase of Parkinson’s disease (PD), are usually overlooked. Carriers of the G2019S LRRK2 mutation are known to be at high risk for developing PD, compared to non-carriers. In this work we aimed to study early changes in Dopamine uptake in non-manifesting PD carriers (NMC) of the G2019S LRRK2 mutation using quantitative DaT-SPECT analysis and to examine the potential for early prediction of PD. Eighty Ashkenazi-Jewish subjects were included in this study: eighteen patients with PD; thirty-one NMC and thirty-one non-manifesting non-carriers (NMNC). All subjects underwent a through clinical assessment including evaluation of motor, olfactory, affective and non-motor symptoms and DaT-SPECT imaging. A population based DaT-SPECT template was created based on the NMNC cohort, and data driven volumes-of-interest (VOIs) were defined. Comparisons between groups were performed based on VOIs and voxel-wise analysis. The striatum area of all three cohorts was segmented into four VOIs, corresponding to the right/left dorsal and ventral striatum. Significant differences in clinical measures were found between patients with PD and non-manifesting subjects with no differences between NMC and NMNC. Significantly lower uptake (p

Gamma knife radiosurgery (GK-RS) is a technique applied in selected cases of mesial-temporal epilepsy, although still limited to centres with adequate instrumentation and expertise. Here, we report a case of radio surgery targeted with the aid of electrical source imaging that localizes the cortical area generating the scalp epileptic discharges. The patient, a 39-year-old male, presented with a right mesio-temporal lesion; electrical source imaging localization partially overlapped with the lesional area but showed an important activation of the omolateral frontal area, concordant with the epileptic network. The patient underwent GK-RS, with good neurosurgical and clinical results. A radiosurgical ellipsoidal treatment volume area of 2 × 2 × 2 cm³, located over the right temporo-mesial region within a centre showing abnormal signal intensity, was considered. Seven months after treatment, the patient developed brain oedema that gradually resolved after one year. After three years of follow-up, the patient was seizure-free (Engel class I). Our very preliminary experience suggests that electrical source imaging appears to be a useful supporting tool for the definition of the radiosurgical treatment volume in selected patients with temporo-mesial lesional epilepsy.

Background Treatment with bevacizumab is associated with substantial radiologic response in patients with glioblastoma (GB). However, following this initial response, changes in T 2 -weighted MRI signal may develop, suggesting an infiltrative pattern of tumor progression. The aim of this study was to differentiate between vasogenic-edema versus tumor-infiltrative area in GB patients. Methods and materials Fourteen patients with GB were longitudinally scanned, before and during intravenous bevacizumab therapy (5/10mg/kg every 2-weeks). A total of 40 MR scans including conventional, diffusion, dynamic susceptibility contrast, dynamic contrast enhancement imaging, and MR-spectroscopy (MRS) were analyzed. Classification of non-enhancing fluid-attenuation-inversion-recovery (FLAIR) area was performed based on mean diffusivity, cerebral blood volume and flow maps, and further characterized using multiple MRI parameters. Results The non-enhancing FLAIR lesion area was classified into: vasogenic-edema , characterized by reduced perfusion and increased FLAIR values; or tumor-infiltrative area, characterized by increased perfusion. Tumor-infiltrative area demonstrated a higher malignant pattern on MRS compared to areas of vasogenic-edema. Substantial reductions of the enhanced T 1 -weighted (58±10%) and hyperintense FLAIR (53±9%) lesion volumes were detected mainly during the first weeks of therapy, with a shift to an infiltrative pattern of tumor progression thereafter, as detected by an increase in tumor-infiltrative area in the majority of patients, which correlated with progression-free survival (week 8: r =−0.86, p =0.003, week 16: r =−0.99, p =0.001). Conclusion Characterization of non-enhancing hyperintense FLAIR lesion area in GB patients can provide an MR-based biomarker, indicating a shift to an infiltrative progression pattern, and may improve therapy response assessment in patients following bevacizumab therapy.

Background and Purpose— Inflammation may contribute to cognitive impairment after stroke. Inflammatory markers are associated with hippocampal atrophy. We tested whether markers of inflammation, erythrocyte sedimentation rate (ESR), and serum levels of C-reactive protein are associated with reduced hippocampal volume and poor cognitive performance among stroke survivors. Methods— We analyzed 368 consecutive cases from our prospective study of first-ever mild–moderate stroke patients. MRI, cognitive tests, and inflammatory markers were determined. Patients were reevaluated 6 and 12 months after the event. Results— ESR remained unchanged in follow-up examinations, suggesting a chronic inflammation background in some patients. Higher levels of C-reactive protein and ESR were associated with worse performance in cognitive tests, particularly memory scores. This association was maintained for ESR (but not C-reactive protein) after adjustment for confounders ( P =0.002). Patients with smaller hippocampi had inferior cognitive results. Moreover, in a multivariate regression model, higher ESR values (but not C-reactive protein) were related to reduced hippocampal volume ( P =0.049). Conclusions— This report shows a strong relationship between ESR and hippocampal volume, as well as with cognitive performance among poststroke patients. This could plausibly relate to incipient cognitive decline via hippocampal pathways.

Aim This study investigated the effects of a theme-based (‘magic’) variation of the hand–arm bimanual intensive therapy programme, in two different countries, in improving activity performance for children with hemiplegia, including those with severe movement restrictions. Method Twenty-three children with spastic hemiplegia (13 males, 10 females; mean age 10y 7mo, range 7–15y; Manual Ability Classification System level I, two; level II, 13; level III, eight), participated in one of three, 2-week, summer camps. A within-participant experimental design was used with the Assisting Hand Assessment and Children's Hand Experience Questionnaire as primary outcome measures. Evaluations occurred immediately before the first day, on the last day, and 3 months after intervention. Two groups underwent additional assessments 2 weeks before the camp. Results Significant intervention effects were seen on the Assisting Hand Assessment (p=0.002) and on the Children's Hand Experience Questionnaire (p

Blood oxygenation level dependence (BOLD) imaging under either hypercapnia or hyperoxia has been used to study neuronal activation and for assessment of various brain pathologies. We evaluated the benefit of a combined protocol of BOLD imaging during both hyperoxic and hypercapnic challenges (termed hemodynamic response imaging (HRI)). Nineteen healthy controls and seven patients with primary brain tumors were included: six with glioblastoma (two newly diagnosed and four with recurrent tumors) and one with atypical-meningioma. Maps of percent signal intensity changes (ΔS) during hyperoxia (carbogen; 95%O2+5%CO2) and hypercapnia (95%air+5%CO2) challenges and vascular reactivity mismatch maps (VRM; voxels that responded to carbogen with reduced/absent response to CO2) were calculated. VRM values were measured in white matter (WM) and gray matter (GM) areas of healthy subjects and used as threshold values in patients. Significantly higher response to carbogen was detected in healthy subjects, compared to hypercapnia, with a GM/WM ratio of 3.8 during both challenges. In patients with newly diagnosed/treatment-naive tumors (n = 3), increased response to carbogen was detected with substantially increased VRM response (compared to threshold values) within and around the tumors. In patients with recurrent tumors, reduced/absent response during both challenges was demonstrated. An additional finding in 2 of 4 patients with recurrent glioblastoma was a negative response during carbogen, distant from tumor location, which may indicate steal effect. In conclusion, the HRI method enables the assessment of blood vessel functionality and reactivity. Reference values from healthy subjects are presented and preliminary results demonstrate the potential of this method to complement perfusion imaging for the detection and follow up of angiogenesis in patients with brain tumors.

Plexiform neurofibromas (PNs) are a major manifestation of neurofibromatosis-1 (NF1), a common genetic disease involving the nervous system. Treatment decisions are mostly based on a gross assessment of changes in tumor using MRI. Accurate volumetric measurements are rarely performed in this kind of tumors mainly due to its great dispersion, size, and multiple locations. This paper presents a semi-automatic method for segmentation of PN from STIR MRI scans. The method starts with a user-based delineation of the tumor area in a single slice and automatically segments the PN lesions in the entire image based on the tumor connectivity. Experimental results on seven datasets, with lesion volumes in the range of 75–690 ml, yielded a mean absolute volume error of 10 % (after manual adjustment) as compared to manual segmentation by an expert radiologist. The mean computation and interaction time was 13 versus 63 min for manual annotation.

E. Kliper, E. Ben Assayag, S. Shenhar-Tsarfaty, L. Shopin, H. Hallevi, E. Uriel, A. Korczyn A, N. M. Bornstein, T. Hendler, O. Aizenstein, and D. Ben Bashat D The Wohl institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Departments of Neurology, Tel Aviv Sourasky Medical Center, Israel, Israel, Departments of Radiology, Tel Aviv Sourasky Medical Center, Israel, Israel, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Israel, Israel

Amyloidoma is a term referring to a tumor-like deposition of extracellular insoluble fibrillar protein. Tumor-like amyloid formation in the brain had been described in isolated cases. However no advanced radiological studies to characterize these lesions have been reported. In the report, we have describe a 59-year-old woman, presented several months prior to diagnosis with memory decline, dizziness, walking instability, and speech difficulties. MRI revealed a left basal ganglia lesion with an intraventricular component. The patient underwent a stereotactic biopsy, which confirmed the diagnosis of amyloidoma, an extensive radiographic characterization of amyloidoma using advanced MR techniques was done, including magnetic resonance spectroscopy, dynamic susceptibility contrast, susceptibility weighted image (SWI), and magnetization transfer (MTR). All advanced MR techniques were able to characterize the amyloidoma as a non-neoplastic process. This is an example where such methods can be used for differential diagnosis of atypical brain lesions.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disorder of the central nervous system (CNS). Differentiating ADEM from other inflammatory disorders, such as multiple sclerosis, is not always conclusive using conventional MRI. To evaluate longitudinal magnetic resonance spectroscopy (MRS) changes that distinguish ADEM from other inflammatory disorders. MRI/MRS scans were performed in seven patients with ADEM during the acute and chronic phases of the disease. Partial recovery was detected between the acute and chronic phases in choline/creatine ratio. Major elevation of lipids and reduction in myo-inositol/creatine ratio was detected in all patients during the acute phase, followed by a reduction in lipids peak and elevation above normal in myo-inositol/creatine ratio during the chronic phase. Consistent and unique MRS changes in metabolite ratios between the acute and chronic presentations of the disease were found. To the best of our knowledge, these patterns have not been described in other inflammatory disorders and might assist in the early diagnosis of ADEM.

Advanced MR imaging methods have an essential role in classification, grading, follow-up and therapeutic management in patients with brain tumors. With the introduction of new therapeutic options, the challenge for better tissue characterization and diagnosis increase, calling for new reliable non-invasive imaging methods. In the current study we evaluated the added value of a combined protocol of blood oxygen level dependent (BOLD) imaging during hyperoxic challenge (termed hemodynamic response imaging (HRI)) in an orthotopic mouse model for glioblastoma under anti-angiogenic treatment with B20-4.1.1, an anti-VEGF antibody. In glioblastoma tumors, the elevated HRI indicated progressive angiogenesis as further confirmed by histology. In the current glioblastoma model, B20-treatment caused delayed tumor progression with no significant changes in HRI yet with slightly reduced tumor vascularity as indicated by histology. Furthermore, fewer apoptotic cells and higher proliferation index were detected in the B20-treated tumors compared to control-treated tumors. In conclusion, HRI provides an easy, safe and contrast agent free method for the assessment of the brain hemodynamic function, an additionally important clinical information.

Background & AimsWe investigated the effects of the fatty acid–bile acid conjugate 3β-arachidyl-amido, 7α-12α-dihydroxy, 5β-cholan-24-oic acid (Aramchol; Trima Israel Pharmaceutical Products Ltd, Maabarot, Israel) in a phase 2 trial of patients with nonalcoholic fatty liver disease (NAFLD).MethodsWe performed a randomized, double-blind, placebo-controlled trial of 60 patients with biopsy-confirmed NAFLD (6 with nonalcoholic steatohepatitis) at 10 centers in Israel. Patients were given Aramchol (100 or 300 mg) or placebo once daily for 3 months (n = 20/group). The main end point was the difference between groups in the change in liver fat content according to magnetic resonance spectroscopy. The secondary end points focused on the differences between groups in alterations of liver enzyme levels, levels of adiponectin, homeostasis model assessment scores, and endothelial function.ResultsNo serious or drug-related adverse events were observed in the 58 patients who completed the study. Over 3 months, liver fat content decreased by 12.57% ± 22.14% in patients given 300 mg/day Aramchol, but increased by 6.39% ± 36.27% in the placebo group (P = .02 for the difference between groups, adjusted for age, sex, and body mass index). Liver fat content decreased in the 100-mg Aramchol group, by 2.89% ± 28.22%, but this change was nonsignificant (P = .35), indicating a dose–response relationship (P for trend = .01). Groups given Aramchol had nonsignificant improvements over time in endothelial function and levels of alanine aminotransferase and adiponectin, but homeostasis model assessment scores did not change. The appropriateness of a single daily dose was confirmed by pharmacokinetic analysis.ConclusionsThree months' administration of the fatty acid–bile acid conjugate Aramchol is safe, tolerable, and significantly reduces liver fat content in patients with NAFLD. The reduction in liver fat content occurred in a dose-dependent manner and was associated with a trend of metabolic improvements, indicating that Aramchol might be used for the treatment of fatty liver disease. ClinicalTrials.gov number: NCT01094158.

Background and purposeStroke is a major cause of cognitive impairment and dementia in adults, however the role of the ischemic lesions themselves, on top of other risk factors known in the elderly, remains controversial. This study used structural equation modeling to determine the respective impact of the new ischemic lesions' volume, preexisting white matter lesions and white matter integrity on post stroke cognitive state.MethodsConsecutive first ever mild to moderate stroke or transient ischemic attack patients recruited into the ongoing prospective TABASCO study underwent magnetic resonance imaging scans within seven days of stroke onset and were cognitively assessed one year after the event using a computerized neuropsychological battery. The volumes of both ischemic lesions and preexisting white matter lesions and the integrity of the normal appearing white matter tissue were measured and their contribution to cognitive state was assessed using structural equation modeling path analysis taking into account demographic parameters. Two models were hypothesized, differing by the role of ischemic lesions' volume.ResultsStructural equation modeling analysis of 142 patients confirmed the predominant role of white matter lesion volume (standardized path coefficient β = -0.231) and normal appearing white matter integrity (β = -0.176) on the global cognitive score, while ischemic lesions' volume showed no such effect (β = 0.038). The model excluding the ischemic lesion presented better fit to the data (comparative fit index 0.9 versus 0.092).ConclusionsMild to moderate stroke patients with preexisting white matter lesions are more vulnerable to cognitive impairment regardless of their new ischemic lesions. Thus, these patients can serve as a target group for studies on cognitive rehabilitation and neuro-protective therapies which may, in turn, slow their cognitive deterioration.

Purpose: Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans. Methods: The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a “gold standard” was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution. Results: Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard. Conclusions: The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior.

The neonatal period is considered to be essential for neurodevelopment and wellbeing throughout the life span, yet little is known about brain–behavior relationships in the neonatal period. The aim of this study was to evaluate the association between neonatal sensory–motor regulation and white-matter (WM) integrity of major fiber tracts in the neonatal period. We hypothesized that WM integrity of sensory–motor systems would predict neurobehavioral maturation during the first month of life.Forty-nine premature neonates underwent magnetic-resonance-imaging at term. Diffusion-tensor-imaging analysis was performed in major WM tracts along with repeated neonatal neurobehavioral evaluations assessing sensory reactivity and motor regulation.Difficulties in one or more behavioral sub-category, mostly in auditory and visual attention, hypotonicity and jitteriness, were documented in 78.3% infants at term. Sixty-six percent of infants experienced difficulties, mostly in auditory attention, head–neck control, hypotonicity and motor asymmetry, at 44 weeks.Attention difficulties were associated with reduced integrity of cerebral and superior cerebellar peduncles; while tonicity was associated with reduced integrity of the corpus-callosum and inferior–posterior tracts. Overall, results showed that early maturing tracts were related with the degree of typicality of sensory reactivity status while late maturing tracts were related with the degree of typicality of tonic regulation. WM integrity and maturation factors explained 40.2% of the variance in neurobehavior at 44 weeks.This study suggests that in preterm neonates, deviant sensory–motor reactivity can be detected very early in development in manners that are related to lower integrity/maturational level of early and late maturing fiber tracts.