Reduced gyrification in fetal growth restriction with prenatal magnetic resonance images.

Placental-related fetal growth restriction, resulting from placental dysfunction, impacts 3-5% of pregnancies and is linked to elevated risk of adverse neurodevelopmental outcomes. In response, the fetus employs a mechanism known as brain-sparing, redirecting blood flow to the cerebral circuit, for adequate supply to the brain. In this study we aimed to quantitatively evaluate disparities in gyrification and brain volumes among fetal growth restriction, small for gestational age and appropriate-for gestational-age fetuses. Additionally, we compared fetal growth restriction fetuses with and without brain-sparing. The study encompassed 106 fetuses: 35 fetal growth restriction (14 with and 21 without brain-sparing), 8 small for gestational age, and 63 appropriate for gestational age. Gyrification, supratentorial, and infratentorial brain volumes were automatically computed from T2-weighted magnetic resonance images, following semi-automatic brain segmentation. Fetal growth restriction fetuses exhibited significantly reduced gyrification and brain volumes compared to appropriate for gestational age (P < 0.001). Small for gestational age fetuses displayed significantly reduced gyrification (P = 0.038) and smaller supratentorial volume (P < 0.001) compared to appropriate for gestational age. Moreover, fetal growth restriction fetuses with BS demonstrated reduced gyrification compared to those without BS (P = 0.04), with no significant differences observed in brain volumes. These findings demonstrate that brain development is affected in fetuses with fetal growth restriction, more severely than in small for gestational age, and support the concept that vasodilatation of the fetal middle cerebral artery reflects more severe hypoxemia, affecting brain development.

The natural history study of preclinical genetic Creutzfeldt-Jakob Disease (CJD): a prospective longitudinal study protocol.

BACKGROUND: Creutzfeldt-Jakob Disease (CJD) is the most common prion disease in humans causing a rapidly progressive neurological decline and dementia and is invariably fatal. The familial forms (genetic CJD, gCJD) are caused by mutations in the PRNP gene encoding for the prion protein (PrP). In Israel, there is a large cluster of gCJD cases, carriers of an E200K mutation in the PRNP gene, and therefore the largest population of at-risk individuals in the world. The mutation is not necessarily sufficient for the formation and accumulation of the pathological prion protein (PrPsc), suggesting that other, genetic and non-genetic factors affect the age at symptoms onset. Here we present the protocol of a cross-sectional and longitudinal natural history study of gCJD patients and first-degree relatives of gCJD patients, aiming to identify biological markers of preclinical CJD and risk factors for phenoconversion. METHODS: The study has two groups: Patients diagnosed with gCJD, and first-degree healthy relatives (HR) (both carriers and non-carriers of the E200K mutation in the PRNP gene) of patients diagnosed with gCJD. At baseline, and at the end of every year, healthy participants are invited for an "in-depth" visit, which includes a clinical evaluation, blood and urine collection, gait assessment, brain MRI, lumbar puncture (LP), and Polysomnography (PSG). At 6 months from baseline, and then halfway through each year, participants are invited for a "brief" visit, which includes a clinical evaluation, short cognitive assessment, and blood and urine collection. gCJD patients will be invited for one "in-depth" visit, similar to the baseline visit of healthy relatives. DISCUSSION: This continuous follow-up of the participants and the frequent assessments will allow early identification and diagnosis in case of conversion into disease. The knowledge generated from this study is likely to advance the understanding of the underlying clinicopathological processes that occur at the very beginning of CJD, as well as potential genetic and environmental risk factors for the development of the disease, therefore advancing the development of safe and efficient interventions. TRIAL REGISTRATION: The study is an observational study. It has registered retrospectively in https://clinicaltrials.gov/ and has been assigned an identification number NCT05746715.

Optimization of two-compartment-exchange-model analysis for dynamic contrast-enhanced mri incorporating bolus arrival time.

PURPOSE: To optimize the analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) under the two-compartment-exchange-model (2CXM) and to incorporate voxelwise bolus-arrival-time (BAT). MATERIALS AND METHODS: The accuracy of the pharmacokinetic (PK) parameters, extracted from 3T DCE-MRI using 2CXM, was tested under several conditions: eight algorithms for data estimation; correction for BAT; using model selection; different temporal resolution and scan duration. Comparisons were performed on simulated data. The best algorithm was applied to seven patients with brain tumors or following stroke. The extracted perfusion parameters were compared to those of dynamic susceptibility contrast MRI (DSC-MRI). RESULTS: ACoPeD (AIF-corrected-perfusion-DCE-MRI), an analysis using a 2nd derivative regularized-spline and incorporating BAT, achieved the most accurate estimation in simulated data, mean-relative-error: Fp , F, vp , ve : 24.8%, 41.7%, 26.4%, 27.2% vs. 76.5%, 190.8%, 78.8%, 82.39% of the direct four parameters estimation (one-sided two-sample t-test, P < 0.001). Correction for BAT increased the estimation accuracy of the PK parameters by more than 30% and provided a supertemporal resolution estimation of the BAT (higher than the acquired resolution, mean-absolute-error 0.2 sec). High temporal resolution (∼2 sec) is required to avoid biased estimation of PK parameters, and long scan duration (∼20 min) is important for reliable permeability but not for perfusion estimations, mean-error-reduction: E: ∼12%, ve : ∼6%. Using ACoPeD, PK values from normal-appearing white matter, gray matter, and lesion were extracted from patients. Preliminary results showed significant voxelwise correlations to DSC-MRI, between flow values in a patient following stroke (r = 0.49, P < 0.001), and blood volume in a patient with a brain tumor (r = 0.62, P < 0.001). CONCLUSION: This study proposes an optimized analysis method, ACoPeD, for tissue perfusion and permeability estimation using DCE-MRI, to be used in clinical settings. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:237-249.

Diffuse excessive high signal intensity in low-risk preterm infants at term-equivalent age does not predict outcome at 1 year: a prospective study.

INTRODUCTION: The outcome of premature infants with only diffuse excessive high signal intensity (DEHSI) is not clear. We explored the relationship between DEHSI, white matter (WM) diffusion characteristics, perinatal characteristics, and neurobehavioral outcome at 1 year in a homogenous group of preterm infants without major brain abnormalities. METHODS: Fifty-eight preterm infants, gestational age 29 ± 2.6 weeks, underwent an MRI at term-equivalent age (TEA). Griffiths Mental Developmental Scales, neurological assessment, and Parental Stress Index (PSI) were performed at 1 year corrected age. These measures were compared between preterm infants according to DEHSI classification (none, mild, moderate). Diffusion tensor imaging was used in major WM volumes of interest to objectively measure the degree of WM maturation. RESULTS: No significant differences were detected in the perinatal risk characteristics, neurobehavioral outcome, and PSI at 1 year between infants with different DEHSI classifications. In infants with DEHSI, increased axial and radial diffusivities were detected in the optic radiations, centrum semiovale, and posterior limb of the internal capsule, indicating less advanced maturation of the WM. Significant correlations were detected between the time interval from birth to MRI and the WM microstructure in infants without DEHSI. CONCLUSION: DEHSI in premature infants is neither a predictive measure for short-term adverse neurobehavioral outcome nor related to perinatal risk characteristics. Extrauterine exposure time had a differential effect on WM maturational trajectories in infants with DEHSI compared to those without. We suggest DEHSI may represent an alteration in WM maturational characteristics. Further follow-up studies may verify later consequences of DEHSI in premature infants.

The use of electrical source imaging in targeting lesional mesial temporal epilepsy for radiosurgical treatment.

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.

Cognitive decline after stroke: relation to inflammatory biomarkers and hippocampal volume.

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.

Fetal brain tissue annotation and segmentation challenge results.

In-utero fetal MRI is emerging as an important tool in the diagnosis and analysis of the developing human brain. Automatic segmentation of the developing fetal brain is a vital step in the quantitative analysis of prenatal neurodevelopment both in the research and clinical context. However, manual segmentation of cerebral structures is time-consuming and prone to error and inter-observer variability. Therefore, we organized the Fetal Tissue Annotation (FeTA) Challenge in 2021 in order to encourage the development of automatic segmentation algorithms on an international level. The challenge utilized FeTA Dataset, an open dataset of fetal brain MRI reconstructions segmented into seven different tissues (external cerebrospinal fluid, gray matter, white matter, ventricles, cerebellum, brainstem, deep gray matter). 20 international teams participated in this challenge, submitting a total of 21 algorithms for evaluation. In this paper, we provide a detailed analysis of the results from both a technical and clinical perspective. All participants relied on deep learning methods, mainly U-Nets, with some variability present in the network architecture, optimization, and image pre- and post-processing. The majority of teams used existing medical imaging deep learning frameworks. The main differences between the submissions were the fine tuning done during training, and the specific pre- and post-processing steps performed. The challenge results showed that almost all submissions performed similarly. Four of the top five teams used ensemble learning methods. However, one team's algorithm performed significantly superior to the other submissions, and consisted of an asymmetrical U-Net network architecture. This paper provides a first of its kind benchmark for future automatic multi-tissue segmentation algorithms for the developing human brain in utero.

Aberrant dopamine transporter and functional connectivity patterns in LRRK2 and GBA mutation carriers.

Non-manifesting carriers (NMCs) of Parkinson's disease (PD)-related mutations such as LRRK2 and GBA are at an increased risk for developing PD. Dopamine transporter (DaT)-spectral positron emission computed tomography is widely used for capturing functional nigrostriatal dopaminergic activity. However, it does not reflect other ongoing neuronal processes; especially in the prodromal stages of the disease. Resting-state fMRI (rs-fMRI) has been proposed as a mode for assessing functional alterations associated with PD, but its relation to dopaminergic deficiency remains unclear. We aimed to study the association between presynaptic striatal dopamine uptake and functional connectivity (FC) patterns among healthy first-degree relatives of PD patients with mutations in LRRK2 and GBA genes. N = 85 healthy first-degree subjects were enrolled and genotyped. All participants underwent DaT and rs-fMRI scans, as well as a comprehensive clinical assessment battery. Between-group differences in FC within striatal regions were investigated and compared with striatal binding ratios (SBR). N = 26 GBA-NMCs, N = 25 LRRK2-NMCs, and N = 34 age-matched nonmanifesting noncarriers (NM-NCs) were included in each study group based on genetic status. While genetically-defined groups were similar across clinical measures, LRRK2-NMCs demonstrated lower SBR in the right putamen compared with NM-NCs, and higher right putamen FC compared to GBA-NMCs. In this group, higher striatal FC was associated with increased risk for PD. The observed differential SBR and FC patterns among LRRK2-NMCs and GBA-NMCs indicate that DaTscan and FC assessments might offer a more sensitive prediction of the risk for PD in the pre-clinical stages of the disease.

Preventing post-stroke dementia. The MARCH Trial. Protocol and statistical analysis plan of a randomized clinical trial testing the safety and efficacy of Maraviroc in post-stroke cognitive impairment.

Background: Current evidence suggest that 25%-33% of stroke-survivors develop post-stroke cognitive impairment (PSCI). The licensed drug Maraviroc, a CCR5-antagonist, is postulated to act via a neuroprotective mechanism that may offer the potential of preventing progression to vascular dementia. Our hypothesis: Maraviroc may have the potential to augment learning skills and cognitive performance by affecting synaptic plasticity, along with neuro-inflammatory modulation in patients with cerebral small vessel disease (SVD) and PSCI. Design: MARCH is a multi-center, double-blind randomized-control Phase-II trial of Maraviroc 150 or 600 mg/day versus placebo for 12-months in five stroke centers in Israel. Included are patients diagnosed with recent (1-24 months) subcortical stroke who experience mild PSCI and have evidence of white matter lesions and SVD on neuroimaging. Outcomes: Primary outcomes: 1. Change in cognitive scores. 2. Drug related adverse events. Secondary outcomes: change in functional and affective scores, MRI-derived measures, inflammatory markers, carotid atherosclerosis, cerebrospinal-fluid biomarkers in a sub-study. A sample size of 60 in each treatment group and 30 in the placebo group (total - 150 participants) provides 80% power between the treatment and the placebo groups. Conclusions: The results of this work could lead to a novel, readily available, therapeutic avenue to reduce PSCI, and possibly other pathologies. This study will test safety and effectiveness of Maraviroc in limiting cognitive deterioration and/or post stroke cognitive impairment in patients with cerebral small vessel disease. Schedule: First-patient first-visit was May 2021. Recruitment to complete in 2023, follow-up to complete in 2024.

Fetal Ventriculomegaly and Hydrocephalus - What Shouldn't be Missed on Imaging?

Fetal ventriculomegaly is one of the most frequently diagnosed abnormalities detected prenatally. The finding of additional subtle abnormalities can facilitate accurate prognoses, which may range from normal outcomes to significant neurodevelopmental sequelae. Pathogenesis and imaging patterns of ventriculomegaly and hydrocephalus in the fetus based on the pattern-recognition approach using fetal MRI are reviewed in this paper. This radiological approach may shed light on clinical course prediction and therapeutic efficacy of hydrocephalus in the fetus.

Virtual biopsy using MRI radiomics for prediction of BRAF status in melanoma brain metastasis.

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.

Monitoring brain tumor vascular heamodynamic following anti-angiogenic therapy with advanced magnetic resonance imaging in mice.

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.

Semiautomatic segmentation and follow-up of multicomponent low-grade tumors in longitudinal brain MRI studies.

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.

Interhemispheric and intrahemispheric connectivity and manual skills in children with unilateral cerebral palsy.

This study investigated patterns of motor brain activation, white matter (WM) integrity of inter- and intrahemispheric connectivity and their associations with hand function in children with unilateral cerebral palsy (CP-U). Fourteen CP-U (mean age 10.6 ± 2.7 years) and 14 typically developing children (TDC) underwent magnetic resonance imaging. CP-U underwent extensive motor evaluation. Pattern of brain activation during a motor task was studied in 12 CP-U and six TDC, by calculating laterality index (LI) and percent activation in the sensorimotor areas (around the central sulcus), and quantifying the activation in the supplementary motor area (SMA). Diffusivity parameters were measured in CP-U and eight other TDC for the corpus callosum (CC), affected and less affected cortico-spinal tracts (CST), and posterior limb of the internal capsule (PLIC). Abnormal patterns of brain activation were detected in areas around the central sulcus in 9/12 CP-U, with bilateral activation and/or reduced percent activation. More activation in areas around the central sulcus of the affected hemisphere was associated with better hand function. CP-U demonstrated more activation in the SMA when moving the affected hand compared to the less affected hand. CP-U displayed reduced WM integrity compared to TDC, in the midbody and splenium of the CC, affected CST and affected PLIC. WM integrity in these tracts was correlated with hand function. While abnormal pattern of brain activation was detected mainly when moving the affected hand, the integrity of the CC was correlated with function of both hands and bimanual skills. This study highlights the importance of interhemispheric connectivity for hand function in CP-U, which may have clinical implications regarding prognosis and management.

Brain diffusivity in infants with hypoxic-ischemic encephalopathy following whole body hypothermia: preliminary results.

Hypoxic-ischemic encephalopathy is an important cause of neuropsychological deficits. Little is known about brain diffusivity in these infants following cooling and its potential in predicting outcome. Diffusion tensor imaging was applied to 3 groups: (1) three infants with hypoxic-ischemic encephalopathy: cooled; (2) three infants with hypoxic-ischemic encephalopathy: noncooled; and (3) four controls. Diffusivity values at the corticospinal tract, thalamus, and putamen were correlated with Apgar scores and early neurodevelopmental outcome. While cooled infants exhibited lower Apgar scores than noncooled infants, their developmental scores at a mean age of 8 months were higher. All groups differed in their diffusivity values with the cooled infants showing better values compared with the noncooled, correlating with early neurodevelopmental outcome. These preliminary results indicate that diffusion tensor imaging performed at an early age in infants with hypoxic-ischemic encephalopathy may forecast clinical outcome and support the neuroprotective effect of hypothermia treatment.

The role of advanced MR methods in the diagnosis of cerebral amyloidoma.

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.