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OBJECTIVE Maximal safe resection is the goal of surgical treatment for high-grade glioma (HGG). Deep-seated hemispheric gliomas present a surgical challenge due to safety concerns and previously were often considered inoperable. The authors hypothesized that use of tubular retractors would allow resection of deep-seated gliomas with an acceptable safety profile. The purpose of this study was to describe surgical outcomes and survival data after resection of deep-seated HGG with stereotactically placed tubular retractors, as well as to discuss the technical advances that enable such procedures. METHODS This is a retrospective review of 20 consecutive patients who underwent 22 resections of deep-seated hemispheric HGG with the Viewsite Brain Access System by a single surgeon. Patient demographics, survival, tumor characteristics, extent of resection (EOR), and neurological outcomes were recorded. Cannulation trajectories and planned resection volumes depended on the relative location of white matter tracts extracted from diffusion tractography. The surgical plans were designed on the Brainlab system and preoperatively visualized on the Surgical Theater virtual reality SNAP platform. Volumetric assessment of EOR was obtained on the Brainlab platform and confirmed by a board-certified neuroradiologist. RESULTS Twenty adult patients (18 with IDH–wild-type glioblastomas and 2 with IDH-mutant grade IV astrocytomas) and 22 surgeries were included in the study. The cohort included both newly diagnosed (n = 17; 77%) and recurrent (n = 5; 23%) tumors. Most tumors (64%) abutted the ventricular system. The average preoperative and postoperative tumor volumes measured 33.1 ± 5.3 cm3 and 15.2 ± 5.1 cm3, respectively. The median EOR was 93%. Surgical complications included 2 patients (10%) who developed entrapment of the temporal horn, necessitating placement of a ventriculoperitoneal shunt; 1 patient (5%) who suffered a wound infection and pulmonary embolus; and 1 patient (5%) who developed pneumonia. In 2 cases (9%) patients developed new permanent visual field deficits, and in 5 cases (23%) patients experienced worsening of preoperative deficits. Preoperative neurological or cognitive deficits remained the same in 9 cases (41%) and improved in 7 (32%). The median overall survival was 14.4 months in all patients (n = 20) and in the newly diagnosed IDH–wild-type glioblastoma group (n = 16). CONCLUSIONS Deep-seated HGGs, which are surgically challenging and frequently considered inoperable, are amenable to resection through tubular retractors, with an acceptable safety profile. Such cytoreductive surgery may allow these patients to experience an overall survival comparable to those with more superficial tumors.

Conventional MR imaging does not discriminate basal ganglia and thalamic internal anatomy well. Radiology reports describe anatomic locations but not specific functional structures. Functional neurosurgery uses indirect targeting based on commissural coordinates or atlases that do not fully account for individual variability. We describe innovative MR imaging sequences that improve the visualization of normal anatomy in this complex brain region and may increase our understanding of basal ganglia and thalamic function. Better visualization also may improve treatments for movement disorders and other emerging functional neurosurgery targets. We aim to provide an accessible review of the most clinically-relevant neuroanatomy within the thalamus and basal ganglia.

Human brainstem internal anatomy is intricate, complex, and essential to normal brain function. The brainstem is affected by stroke, multiple sclerosis, and most neurodegenerative diseases-a 1-mm focus of pathologic condition can have profound clinical consequences. Unfortunately, detailed internal brainstem anatomy is difficult to see with conventional MRI sequences. We review normal brainstem anatomy visualized on widely available clinical 3-T MRI scanners using fast gray matter acquisition T1 inversion recovery, probabilistic diffusion tractography, neuromelanin, and susceptibility-weighted imaging. Better anatomic localization using these recent innovations improves our ability to diagnose, localize, and treat brainstem diseases. We aim to provide an accessible review of the most clinically relevant brainstem neuroanatomy.

Control arms for Fig. 6 experiments AND Potential future approaches.

Purpose: Investigation of clonal heterogeneity may be key to understanding mechanisms of therapeutic failure in human cancer. However, little is known on the consequences of therapeutic intervention on the clonal composition of solid tumors.Experimental Design: Here, we used 33 single cell–derived subclones generated from five clinical glioblastoma specimens for exploring intra- and interindividual spectra of drug resistance profiles in vitro. In a personalized setting, we explored whether differences in pharmacologic sensitivity among subclones could be employed to predict drug-dependent changes to the clonal composition of tumors.Results: Subclones from individual tumors exhibited a remarkable heterogeneity of drug resistance to a library of potential antiglioblastoma compounds. A more comprehensive intratumoral analysis revealed that stable genetic and phenotypic characteristics of coexisting subclones could be correlated with distinct drug sensitivity profiles. The data obtained from differential drug response analysis could be employed to predict clonal population shifts within the naïve parental tumor in vitro and in orthotopic xenografts. Furthermore, the value of pharmacologic profiles could be shown for establishing rational strategies for individualized secondary lines of treatment.Conclusions: Our data provide a previously unrecognized strategy for revealing functional consequences of intratumor heterogeneity by enabling predictive modeling of treatment-related subclone dynamics in human glioblastoma. Clin Cancer Res; 23(2); 562–74. ©2016 AACR.

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Confirmatory subclone selection experiments applying clinical sample BN035.

Patient data. AND Drug and compound details. AND Primer sequences for qRT-PCR.

Background There are multiple tools available to visualize the retinal and choroidal vasculature of the posterior globe. However, there are currently no reliable in vivo imaging techniques that can visualize the entire retrobulbar course of the retinal and ciliary vessels. Purpose To identify and characterize the central retinal artery (CRA) using cone-beam CT (CBCT) images obtained as part of diagnostic cerebral angiography. Materials and Methods In this retrospective study, patients with catheter DSA performed between October 2019 and October 2020 were included if CBCT angiography included the orbit in the field of view. The CBCT angiography data sets were postprocessed with a small field-of-view volume centered in the posterior globe to a maximum resolution of 0.2 mm. The following were evaluated: CRA origin, CRA course, CRA point of penetration into the optic nerve sheath, bifurcation of the CRA at the papilla, visualization of anatomic variants, and visualization of the central retinal vein. Descriptive statistical analysis was performed. Results Twenty-one patients with 24 visualized orbits were included in the analysis (mean age, 55 years ± 15; 14 women). Indications for angiography were as follows: diagnostic angiography (n = 8), aneurysm treatment (n = 6), or other (n = 7). The CRA was identified in all orbits; the origin, course, point of penetration of the CRA into the optic nerve sheath, and termination in the papilla were visualized in all orbits. The average length of the intraneural segment was 10.6 mm (range, 7-18 mm). The central retinal vein was identified in six of 24 orbits. Conclusion Cone-beam CT, performed during diagnostic angiography, consistently demonstrated the in vivo central retinal artery, demonstrating excellent potential for multiple diagnostic and therapeutic applications. © RSNA, 2021 Online supplemental material is available for this article.

Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin’s nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method’s sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures., Small-angle X-ray scattering (SAXS) combines the high tissue penetration of X-rays with specificity to periodic nanostructures. The authors use SAXS tensor tomography (SAXS-TT) on intact mouse and human brain tissue samples, to quantify myelin levels and determine myelin integrity, myelinated axon orientation, and fibre tracts non-destructively.

Image labeling using convolutional neural networks (CNNs) are a template‐free alternative to traditional morphometric techniques. We trained a 3D deep CNN to label the hippocampus and amygdala on whole brain 700 μm isotropic 3D MP2RAGE MRI acquired at 7T. Manual labels of the hippocampus and amygdala were used to (i) train the predictive model and (ii) evaluate performance of the model when applied to new scans. Healthy controls and individuals with epilepsy were included in our analyses. Twenty‐one healthy controls and sixteen individuals with epilepsy were included in the study. We utilized the recently developed DeepMedic software to train a CNN to label the hippocampus and amygdala based on manual labels. Performance was evaluated by measuring the dice similarity coefficient (DSC) between CNN‐based and manual labels. A leave‐one‐out cross validation scheme was used. CNN‐based and manual volume estimates were compared for the left and right hippocampus and amygdala in healthy controls and epilepsy cases. The CNN‐based technique successfully labeled the hippocampus and amygdala in all cases. Mean DSC = 0.88 ± 0.03 for the hippocampus and 0.8 ± 0.06 for the amygdala. CNN‐based labeling was independent of epilepsy diagnosis in our sample (p = .91). CNN‐based volume estimates were highly correlated with manual volume estimates in epilepsy cases and controls. CNNs can label the hippocampus and amygdala on native sub‐mm resolution MP2RAGE 7T MRI. Our findings suggest deep learning techniques can advance development of morphometric analysis techniques for high field strength, high spatial resolution brain MRI., We trained a 3D convolutional neural network to label the hippocampus and amygdala on whole brain 700 μm isotropic 3D MP2RAGE MRI acquired at 7T. Our findings suggest deep learning techniques can advance development of morphometric analysis techniques for high field strength, high spatial resolution brain MRI.

Beta amyloid (A beta) accumulation is the earliest pathological marker of Alzheimer's disease (AD), but early AD pathology also affects white matter (WM) integrity. We performed a cross-sectional study including 44 subjects (23 healthy controls and 21 mild cognitive impairment or early AD patients) who underwent simultaneous PET-MR using 18F-Florbetapir, and were categorized into 3 groups based on Ab burden: A beta- [mean mSUVr = 1.17]. Intergroup comparisons of diffusion MRI metrics revealed significant differences across multiple WM tracts. A beta i group displayed more restricted diffusion (higher fractional anisotropy, radial kurtosis, axonal water fraction, and lower radial diffusivity) than both A beta- and A beta+ groups. This nonmonotonic trend was confirmed by significant continuous correlations between mSUVr and diffusion metrics going in opposite direction for 2 cohorts: pooled A beta-/A beta i and pooled A beta i/A beta+. The transient period of increased diffusion restriction may be due to inflammation that accompanies rising A beta burden. In the later stages of A beta accumulation, neurodegeneration is the predominant factor affecting diffusion. (C) 2020 Elsevier Inc. All rights reserved.

Sudden unexplained death in childhood (SUDC) affects children >1-year-old whose cause of death remains unexplained following comprehensive case investigation and is often associated with hippocampal abnormalities. We prospectively performed systematic neuropathologic investigation in 20 SUDC cases, including (i) autopsy data and comprehensive ancillary testing, including molecular studies, (ii) ex vivo 3T MRI and extensive histologic brain samples, and (iii) blinded neuropathology review by 2 board-certified neuropathologists. There were 12 girls and 8 boys; median age at death was 33.3 months. Twelve had a history of febrile seizures, 85% died during apparent sleep and 80% in prone position. Molecular testing possibly explained 3 deaths and identified genetic mutations in TNNI3, RYR2, and multiple chromosomal aberrations. Hippocampal abnormalities most often affected the dentate gyrus (altered thickness, irregular configuration, and focal lack of granule cells), and had highest concordance between reviewers. Findings were identified with similar frequencies in cases with and without molecular findings. Number of seizures did not correlate with hippocampal findings. Hippocampal alterations were the most common finding on histological review but were also found in possibly explained deaths. The significance and specificity of hippocampal findings is unclear as they may result from seizures, contribute to seizure pathogenesis, or be an unrelated phenomenon.

Combining magnetic resonance imaging (MRI) with 2-deoxy-2-F-fluoro-D-glucose positron emission tomography (FDG-PET) data improve the imaging accuracy for detection of Alzheimer disease and related dementias. Integrated FDG-PET-MRI is a recent technical innovation that allows both imaging modalities to be obtained simultaneously from individual patients with cognitive impairment. This report describes the practical benefits and challenges of using integrated FDG-PET-MRI to support the clinical diagnosis of various dementias. Over the past 7 years, we have performed integrated FDG-PET-MRI on >1500 patients with possible cognitive impairment or dementia. The FDG-PET and MRI protocols are the same as current conventions, but are obtained simultaneously over 25 minutes. An additional Dixon MRI sequence with superimposed bone atlas is used to calculate PET attenuation correction. A single radiologist interprets all imaging data and generates 1 report. The most common positive finding is concordant temporoparietal volume loss and FDG hypometabolism that suggests increased risk for underlying Alzheimer disease. Lobar-specific atrophy and FDG hypometabolism patterns that may be subtle, asymmetric, and focal also are more easily recognized using combined FDG-PET and MRI, thereby improving detection of other neurodegeneration conditions such as primary progressive aphasias and frontotemporal degeneration. Integrated PET-MRI has many practical benefits to individual patients, referrers, and interpreting radiologists. The integrated PET-MRI system requires several modifications to standard imaging center workflows, and requires training individual radiologists to interpret both modalities in conjunction. Reading MRI and FDG-PET together increases imaging diagnostic yield for individual patients; however, both modalities have limitations in specificity.

Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by the aggregation of α-synuclein in glia and neurons. Sirolimus (rapamycin) is an mTOR inhibitor that promotes α-synuclein autophagy and reduces its associated neurotoxicity in preclinical models.To investigate the efficacy and safety of sirolimus in patients with MSA using a futility design. We also analyzed 1-year biomarker trajectories in the trial participants.Randomized, double-blind, parallel group, placebo-controlled clinical trial at the New York University of patients with probable MSA randomly assigned (3:1) to sirolimus (2-6 mg daily) for 48 weeks or placebo. Primary endpoint was change in the Unified MSA Rating Scale (UMSARS) total score from baseline to 48 weeks. (ClinicalTrials.gov NCT03589976).The trial was stopped after a pre-planned interim analysis met futility criteria. Between August 15, 2018 and November 15, 2020, 54 participants were screened, and 47 enrolled and randomly assigned (35 sirolimus, 12 placebo). Of those randomized, 34 were included in the intention-to-treat analysis. There was no difference in change from baseline to week 48 between the sirolimus and placebo in UMSARS total score (mean difference, 2.66; 95% CI, -7.35-6.91; P = 0.648). There was no difference in UMSARS-1 and UMSARS-2 scores either. UMSARS scores changes were similar to those reported in natural history studies. Neuroimaging and blood biomarker results were similar in the sirolimus and placebo groups. Adverse events were more frequent with sirolimus. Analysis of 1-year biomarker trajectories in all participants showed that increases in blood neurofilament light chain (NfL) and reductions in whole brain volume correlated best with UMSARS progression.Sirolimus for 48 weeks was futile to slow the progression of MSA and had no effect on biomarkers compared to placebo. One-year change in blood NfL and whole brain atrophy are promising biomarkers of disease progression for future clinical trials. © 2022 International Parkinson and Movement Disorder Society.

BACKGROUND AND PURPOSE: Diffusion MR imaging sequences essential for clinical neuroradiology imaging protocols may be accelerated with simultaneous multislice acquisitions. We tested whether simultaneous multislice–accelerated diffusion data were clinically equivalent to standard acquisitions. MATERIALS AND METHODS: In this retrospective study, clinical diffusion sequences obtained before and after implementation of 2-slice simultaneous multislice acceleration and an altered diffusion gradient sampling scheme using the same 3T MRI scanner and 20-channel coil (n = 25 per group) were independently and blindly evaluated by 2 neuroradiologists for perceived quality, artifacts, and overall diagnostic utility. Diffusion tractography was performed in 13 patients both with and without 2-slice simultaneous multislice acceleration (b = 0, 1000, 2000 s/mm2; 60 directions). The corticospinal tract and arcuate fasciculus ipsilateral to the lesion were generated using the same ROIs and then blindly assessed by a neurosurgeon for anatomic fidelity, perceived quality, and impact on surgical management. Tract volumes were compared for spatial overlap. RESULTS: Two-slice simultaneous multislice diffusion reduced acquisition times from 141 to 45 seconds for routine diffusion and from 7.5 to 5.9 minutes for diffusion tractography using 3T MR imaging. The simultaneous multislice–accelerated diffusion sequence was rated equivalent for diagnostic utility despite reductions to perceived image quality. Simultaneous multislice–accelerated diffusion tractography was rated clinically equivalent. Dice similarity coefficients between routine and simultaneous multislice–generated corticospinal tract and arcuate fasciculus tract volumes were 0.78 (SD, 0.03) and 0.71 (SD, 0.05), respectively. CONCLUSIONS: Two-slice simultaneous multislice diffusion appeared clinically equivalent for standard acquisitions and diffusion tractography. Simultaneous multislice makes it feasible to acquire higher angular and q-space-resolution diffusion acquisitions required for translating advanced diffusion models into clinical practice.

Diffusion tractography is routinely used to study white matter architecture and brain connectivity in vivo. A key step for successful tractography of neuronal tracts is the correct identification of tract directions in each voxel. Here we propose a fingerprinting-based methodology to identify these fiber directions in Orientation Distribution Functions, dubbed ODF-Fingerprinting (ODF-FP). In ODF-FP, fiber configurations are selected based on the similarity between measured ODFs and elements in a pre-computed library. In noisy ODFs, the library matching algorithm penalizes the more complex fiber configurations. ODF simulations and analysis of bootstrapped partial and whole-brain in vivo datasets show that the ODF-FP approach improves the detection of fiber pairs with small crossing angles while maintaining fiber direction precision, which leads to better tractography results. Rather than focusing on the ODF maxima, the ODF-FP approach uses the whole ODF shape to infer fiber directions to improve the detection of fiber bundles with small crossing angle. The resulting fiber directions aid tractography algorithms in accurately displaying neuronal tracts and calculating brain connectivity., 30 pages, 11 figures

BACKGROUND AND PURPOSE: Diagnostic errors in radiology are classified as perception or interpretation errors. This study determined whether specific conditions differed when perception or interpretation errors occurred during neuroradiology image interpretation. MATERIALS AND METHODS: In a sample of 254 clinical error cases in diagnostic neuroradiology, we classified errors as perception or interpretation errors, then characterized imaging technique, interpreting radiologist9s experience, anatomic location of the abnormality, disease etiology, time of day, and day of the week. Interpretation and perception errors were compared with hours worked per shift, cases read per shift, average cases read per shift hour, and the order of case during the shift when the error occurred. RESULTS: Perception and interpretation errors were 74.8% (n = 190) and 25.2% (n = 64) of errors, respectively. Logistic regression analyses showed that the odds of an interpretation error were 2 times greater (OR, 2.09; 95% CI, 1.05–4.15; P = .04) for neuroradiology attending physicians with ≤5 years of experience. Interpretation errors were more likely with MR imaging compared with CT (OR, 2.10; 95% CI, 1.09–4.01; P = .03). Infectious/inflammatory/autoimmune diseases were more frequently associated with interpretation errors (P = .04). Perception errors were associated with faster reading rates (6.01 versus 5.03 cases read per hour; P = .004) and occurred later during the shift (24th-versus-18th case; P = .04). CONCLUSIONS: Among diagnostic neuroradiology error cases, interpretation-versus-perception errors are affected by the neuroradiologist9s experience, technique, and the volume and rate of cases read. Recognition of these risk factors may help guide programs for error reduction in clinical neuroradiology services.

Background Intramedullary spinal cord neoplasms (ISCN) pose significant management challenges. Advances in magnetic resonance imaging (MRI) (such as diffusion tensor imaging, DTI) have been utilized to determine the infiltrative nature and resectability of ISCN. However, this has not been applied to intraoperative decision making. Objective To present a case series of 2 patients with ISCN, the first to combine use of DTI, pre- and intraoperative 3-dimensional (3D) virtual reality imaging, and microscope integrated navigation with heads-up display. Methods Two patients who underwent surgery for ISCN were included. DTI images were obtained and 3D images were created using Surgical Theater (Surgical Theater SRP, Version 7.4.0, Cleveland, Ohio). Fiducials were used to achieve accurate surface registration to C4. Navigation confirmed the levels of laminectomy necessary. The microscope was integrated with Brainlab (Brainlab AG Version 3.0.5, Feldkirchen, Germany) and the tumor projected in the heads-up display. Surgical Theater was integrated with Brainlab to allow for real time evaluation of the 3D tractography. Results Case 1: All tracts were pushed away from the tumor, suggesting it was not infiltrative. Surgical Theater and Brainlab assisted in confirming midline despite the abnormal swelling of the cord so the myelotomy could be performed. The heads-up display outline demonstrated excellent correlation to the tumor. Gross total resection was achieved. Diagnosis of ependymoma was confirmed. Case 2: Some tracts were going through the tumor itself, suggesting an infiltrative process. Surgical Theater and Brainlab again allowed for confirmation of the midline raphe. Near total resection of the enhancing portion was achieved. Diagnosis of glioblastoma was confirmed. Conclusion This is a proof of concept application where multi-modal imaging technology was utilized for safest maximal ISCN resection.

Background and PurposeHigh-resolution T2-weighted sequences are frequently used in magnetic resonance imaging (MRI) studies to assess the cerebellopontine angle and internal auditory canal (IAC) in sensorineural hearing loss patients but have low yield and lengthened examinations. Because image cont

BACKGROUND: Functional MRI improves preoperative planning in patients with brain tumors, but task-correlated signal intensity changes are only 2%–3% above baseline. This makes accurate functional mapping challenging. Marchenko-Pastur principal component analysis (MP-PCA) provides a novel strategy to separate functional MRI signal from noise without requiring user input or prior data representation. PURPOSE: To determine whether MP-PCA denoising improves activation magnitude for task-based functional MRI language mapping in patients with brain tumors. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act–compliant study, MP-PCA performance was first evaluated by using simulated functional MRI data with a known ground truth. Right-handed, left-language–dominant patients with brain tumors who successfully performed verb generation, sentence completion, and finger tapping functional MRI tasks were retrospectively identified between January 2017 and August 2018. On the group level, for each task, histograms of z scores for original and MP-PCA denoised data were extracted from relevant regions and contralateral homologs were seeded by a neuroradiologist blinded to functional MRI findings. Z scores were compared with paired two-sided t tests, and distributions were compared with effect size measurements and the Kolmogorov-Smirnov test. The number of voxels with a z score greater than 3 was used to measure task sensitivity relative to task duration. RESULTS: Twenty-three patients (mean age ± standard deviation, 43 years ± 18; 13 women) were evaluated. MP-PCA denoising led to a higher median z score of task-based functional MRI voxel activation in left hemisphere cortical regions for verb generation (from 3.8 ± 1.0 to 4.5 ± 1.4; P < .001), sentence completion (from 3.7 ± 1.0 to 4.3 ± 1.4; P < .001), and finger tapping (from 6.9 ± 2.4 to 7.9 ± 2.9; P < .001). Median z scores did not improve in contralateral homolog regions for verb generation (from −2.7 ± 0.54 to −2.5 ± 0.40; P = .90), sentence completion (from −2.3 ± 0.21 to −2.4 ± 0.37; P = .39), or finger tapping (from −2.3 ± 1.20 to −2.7 ± 1.40; P = .07). Individual functional MRI task durations could be truncated by at least 40% after MP-PCA without degradation of clinically relevant correlations between functional cortex and functional MRI tasks. CONCLUSION: Denoising with Marchenko-Pastur principal component analysis led to higher task correlations in relevant cortical regions during functional MRI language mapping in patients with brain tumors. © RSNA, 2020 Online supplemental material is available for this article.

BACKGROUND AND PURPOSE: The brain stem is a complex configuration of small nuclei and pathways for motor, sensory, and autonomic control that are essential for life, yet internal brain stem anatomy is difficult to characterize in living subjects. We hypothesized that the 3D fast gray matter acquisition T1 inversion recovery sequence, which uses a short inversion time to suppress signal from white matter, could improve contrast resolution of brain stem pathways and nuclei with 3T MR imaging. MATERIALS AND METHODS: After preliminary optimization for contrast resolution, the fast gray matter acquisition T1 inversion recovery sequence was performed in 10 healthy subjects (5 women; mean age, 28.8 ± 4.8 years) with the following parameters: TR/TE/TI = 3000/2.55/410 ms, flip angle = 4°, isotropic resolution = 0.8 mm, with 4 averages (acquired separately and averaged outside k-space to reduce motion; total scan time = 58 minutes). One subject returned for an additional 5-average study that was combined with a previous session to create a highest quality atlas for anatomic assignments. A 1-mm isotropic resolution, 12-minute version, proved successful in a patient with a prior infarct. RESULTS: The fast gray matter acquisition T1 inversion recovery sequence generated excellent contrast resolution of small brain stem pathways in all 3 planes for all 10 subjects. Several nuclei could be resolved directly by image contrast alone or indirectly located due to bordering visualized structures (eg, locus coeruleus and pedunculopontine nucleus). CONCLUSIONS: The fast gray matter acquisition T1 inversion recovery sequence has the potential to provide imaging correlates to clinical conditions that affect the brain stem, improve neurosurgical navigation, validate diffusion tractography of the brain stem, and generate a 3D atlas for automatic parcellation of specific brain stem structures.

The authors reviewed the two most common current uses of brain 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET) at a large academic medical center. For epilepsy patients considering surgical management, FDG-PET can help localize epileptogenic lesions, discriminate between multiple or discordant EEG or MRI findings, and predict prognosis for post-surgical seizure control. In elderly patients with cognitive impairment, FDG-PET often demonstrates lobar-specific patterns of hypometabolism that suggest particular underlying neurodegenerative pathologies, such as Alzheimer's disease. FDG-PET of the brain can be a key diagnostic modality and contribute to improved patient care.

Multi-parametric quantitative MRI (qMRI) of the spinal cord is a promising non-invasive tool to probe early microstructural damage in neurological disorders. It is usually performed in vivo by combining acquisitions with multiple signal readouts, which exhibit different thermal noise levels, geometrical distortions and susceptibility to physiological noise. This ultimately hinders joint multi-contrast modelling and makes the geometric correspondence of parametric maps challenging. We propose an approach to overcome these limitations, by implementing state-of-the-art microstructural MRI of the spinal cord with a unified signal readout in vivo (i.e. with matched spatial encoding parameters across a range of imaging contrasts). We base our acquisition on single-shot echo planar imaging with reduced field-of-view, and obtain data from two different vendors (vendor 1: Philips Achieva; vendor 2: Siemens Prisma). Importantly, the unified acquisition allows us to compare signal and noise across contrasts, thus enabling overall quality enhancement via multi-contrast image denoising methods. As a proof-of-concept, here we provide a demonstration with one such method, known as Marchenko-Pastur (MP) Principal Component Analysis (PCA) denoising. MP-PCA is a singular value (SV) decomposition truncation approach that relies on redundant acquisitions, i.e. such that the number of measurements is large compared to the number of components that are maintained in the truncated SV decomposition. Here we used in vivo and synthetic data to test whether a unified readout enables more efficient MP-PCA denoising of less redundant acquisitions, since these can be denoised jointly with more redundant ones. We demonstrate that a unified readout provides robust multi-parametric maps, including diffusion and kurtosis tensors from diffusion MRI, myelin metrics from two-pool magnetisation transfer, and T1 and T2 from relaxometry. Moreover, we show that MP-PCA improves the quality of our multi-contrast acquisitions, since it reduces the coefficient of variation (i.e. variability) by up to 17% for mean kurtosis, 8% for bound pool fraction (BPF, myelin-sensitive), and 13% for T1, while enabling more efficient denoising of modalities limited in redundancy (e.g. relaxometry). In conclusion, multi-parametric spinal cord qMRI with unified readout is feasible and provides robust microstructural metrics with matched resolution and distortions, whose quality benefits from multi-contrast denoising methods such as MP-PCA.

At very low diffusion weighting the diffusion MRI signal is affected by intravoxel incoherent motion (IVIM) caused by dephasing of magnetization due to incoherent blood flow in capillaries or other sources of microcirculation. While IVIM measurements at low diffusion weightings have been frequently used to investigate perfusion in the body as well as in malignant tissue, the effect and origin of IVIM in normal brain tissue is not completely established. We investigated the IVIM effect on the brain diffusion MRI signal in a cohort of 137 radiologically-normal patients (62 male; mean age = 50.2 ± 17.8, range = 18 to 94). We compared the diffusion tensor parameters estimated from a mono-exponential fit at b = 0 and 1000 s/mm2 versus at b = 250 and 1000 s/mm2. The asymptotic fitting method allowed for quantitative assessment of the IVIM signal fraction f* in specific brain tissue and regions. Our results show a mean (median) percent difference in the mean diffusivity of about 4.5 (4.9)% in white matter (WM), about 7.8 (8.7)% in cortical gray matter (GM), and 4.3 (4.2)% in thalamus. Corresponding perfusion fraction f* was estimated to be 0.033 (0.032) in WM, 0.066 (0.065) in cortical GM, and 0.033 (0.030) in the thalamus. The effect of f* with respect to age was found to be significant in cortical GM (Pearson correlation ρ ​= ​0.35, p ​= ​3*10−5) and the thalamus (Pearson correlation ρ = 0.20, p = 0.022) with an average increase in f* of 5.17*10−4/year and 3.61*10−4/year, respectively. Significant correlations between f* and age were not observed for WM, and corollary analysis revealed no effect of gender on f*. Possible origins of the IVIM effect in normal brain tissue are discussed.

Fluorodeoxyglucose (FDG) positron emission tomography-magnetic resonance (PET/MR) is useful for the evaluation of cognitively-impaired patients. This study aims to assess two different attenuation correction (AC) methods (Dixon-MR and atlas-based) versus index-standard computed tomography (CT) AC for the visual interpretation of regional hypometabolism in patients with cognitive impairment. Two board-certified nuclear medicine physicians blindly scored brain region FDG hypometabolism as normal versus hypometabolic using two-dimensional (2D) and 3D FDG PET/MR images generated by MIM software. Regions were quantitatively assessed as normal versus mildly, moderately, or severely hypometabolic. Hypometabolism scores obtained using the different methods of AC were compared, and interreader, as well as intra-reader agreement, was assessed. Regional hypometabolism versus normal metabolism was correctly classified in 16 patients on atlas-based and Dixon-based AC map PET reconstructions (vs. CT reference AC) for 94% (90%–96% confidence interval [CI]) and 93% (89%–96% CI) of scored regions, respectively. The averaged sensitivity/specificity for detection of any regional hypometabolism was 95%/94% (P = 0.669) and 90%/91% (P = 0.937) for atlas-based and Dixon-based AC maps. Interreader agreement for detection of regional hypometabolism was high, with similar outcome assessments when using atlas- and Dixon-corrected PET data in 93% (Κ =0.82) and 93% (Κ =0.84) of regions, respectively. Intrareader agreement for detection of regional hypometabolism was high, with concordant outcome assessments when using atlas- and Dixon-corrected data in 93%/92% (Κ =0.79) and 92/93% (Κ =0.78). Despite the quantitative advantages of atlas-based AC in brain PET/MR, routine clinical Dixon AC yields comparable visual ratings of regional hypometabolism in the evaluation of cognitively impaired patients undergoing brain PET/MR and is similar in performance to CT-based AC. Therefore, Dixon AC is acceptable for the routine clinical evaluation of dementia syndromes.

Summary Malformations of cortical development are associated with epilepsy and cognitive dysfunction, and can occur in patients with SCN1A ion channel mutations. We report a novel and subtle bandlike subcortical heterotopia on integrated positron emission tomography–magnetic resonance imaging ( PET‐MRI) in a patient with treatment‐resistant epilepsy due to a de novo KCNQ1 frameshift mutation. Our case highlights the potential for other channel mutations to cause both epilepsy and cortical malformations. Further scrutiny of high contrast resolution MRI studies is warranted for patients with KCNQ1 and other epilepsy genes to further define their extended phenotype.

Background Clinical orbital MRI protocols are routinely used to study the optic nerves and exclude compressive lesions, infarctions, or inflammation. However, the small caliber and divergent oblique orientations of the optic nerves make it challenging to characterize them well with conventional MRI, especially since adjacent air-filled bony structures distort the MRI signal and motion is a problem even in cooperative, healthy volunteers. Evidence acquisition Over the past 3 years we have experimented with multiple novel MRI approaches and sequences to better characterize the optic nerves. The perfect MRI protocol would be quantitative and sensitive to subtle optic nerve pathologic changes, provide high spatial resolution, be rapidly acquired, and resistant to motion degradation. Results This review provides an update of recent MRI sequence innovations for the optic nerves being currently translated into clinical practice. Methods discussed include rapid MRI with compressed sensing or simultaneous multislice approaches, postprocessing techniques for quantitative T2 mapping or track density imaging, and multiple MRI sequences for measuring diffusion in the optic nerves. Conclusions Recently-developed orbit-specific MRI coils, quantitative sequences, and rapid acquisition techniques can improve our future ability to study optic nerve pathologies noninvasively. As advanced MRI becomes more proficient at characterizing the optic nerves, its role in the clinical management of patients should increase.

Introduction Quantitative T2 mapping may provide an objective biomarker for occult nervous tissue pathology in relapsing-remitting multiple sclerosis (RRMS). We applied a novel echo modulation curve (EMC) algorithm to identify T2 changes in normal-appearing brain regions of subjects with RRMS (N = 27) compared to age-matched controls (N = 38). Methods The EMC algorithm uses Bloch simulations to model T2 decay curves in multi-spin-echo MRI sequences, independent of scanner, and scan-settings. T2 values were extracted from normal-appearing white and gray matter brain regions using both expert manual regions-of-interest and user-independent FreeSurfer segmentation. Results Compared to conventional exponential T2 modeling, EMC fitting provided more accurate estimations of T2 with less variance across scans, MRI systems, and healthy individuals. Thalamic T2 was increased 8.5% in RRMS subjects (p, Highlights • EMC technique provides accurate and scanner-invariant T2 mapping in MS subjects. • Thalamus T2 differences distinguish relapsing-remitting MS subjects from controls. • Normal-appearing brain regions demonstrate T2 changes in MS patients compared to controls. • T2 values reflect anatomic and function-specific differences in healthy controls.

Multi-parametric quantitative MRI (qMRI) of the spinal cord is a promising non-invasive tool to probe early microstructural damage in neurological disorders. It is usually performed by combining acquisitions with multiple signal readouts, which exhibit different thermal noise levels, geometrical distortions and susceptibility to physiological noise. This ultimately hinders joint multi-contrast modelling and makes the geometric correspondence of parametric maps challenging. We propose an approach to overcome these limitations, by implementing state-of-the-art microstructural MRI of the spinal cord with a unified signal readout. We base our acquisition on single-shot echo planar imaging with reduced field-of-view, and obtain data from two different vendors (vendor 1: Philips Achieva; vendor 2: Siemens Prisma). Importantly, the unified acquisition allows us to compare signal and noise across contrasts, thus enabling overall quality enhancement via Marchenko-Pastur (MP) Principal Component Analysis (PCA) denoising. MP-PCA is a recent method relying on redundant acquisitions, i.e. such that the number of measurements is much larger than the number of informative principal components. Here we used in vivo and synthetic data to test whether a unified readout enables more efficient denoising of less redundant acquisitions, since these can be denoised jointly with more redundant ones. We demonstrate that a unified readout provides robust multi-parametric maps, including diffusion and kurtosis tensors from diffusion MRI, myelin metrics from two-pool magnetisation transfer, and T1 and T2 from relaxometry. Moreover, we show that MP-PCA improves the quality of our multi-contrast acquisitions, since it reduces the coefficient of variation (i.e. variability) by up to 15% for mean kurtosis, 8% for bound pool fraction (BPF, myelin-sensitive), and 13% for T1, while enabling more efficient denoising of modalities limited in redundancy (e.g. relaxometry). In conclusion, multi-parametric spinal cord qMRI with unified readout is feasible and provides robust microstructural metrics with matched resolution and distortions, whose quality benefits from MP-PCA denoising, a useful pre-processing tool for spinal cord MRI.

The thalamus consists of several functionally distinct nuclei, some of which serve as targets for functional neurosurgery. Visualization of such nuclei is a major challenge due to their low signal contrast on conventional imaging. We introduce MR susceptibility imaging with a short TE, leveraging susceptibility differences among thalamic nuclei, to automatically delineate 15 thalamic subregions. The technique has the potential to enable direct targeting of thalamic nuclei for functional neurosurgical guidance.

Objectives: Clinically relevant neuroanatomy is challenging to teach, learn and remember since many functionally important structures are visualized best using histology stains from serial 2D planar sections of the brain. In clinical patients, the locations of specific structures then must be inferred from spatial position and surface anatomy. A 3D MRI dataset of neuroanatomy has several advantages including simultaneous multi-planar visualization in the same brain, direct end-user manipulation of the data and image contrast identical to clinical MRI. We created 3D MRI datasets of the postmortem brain with high spatial and contrast resolution for simultaneous multi-planar visualization of complex neuroanatomy. Materials and Methods: Whole human brains (N=5) were immersion-fixed in 4% formaldehyde for 4 weeks, then washed continuously in water for 48 hrs. The brains were imaged on a clinical 3-T MRI scanner with a 64-channel head and neck coil using a 3D turbo spin echo sequence with 400-micron isotropic resolution (voxel = 0.064 mm3; time = 7 hrs). Besides resolution, this sequence has multiple adjustments to improve contrast compared to a clinical protocol, including 93% reduced turbo factor and 77% reduced effective echo time. Results: This MRI microscopy protocol provided excellent contrast resolution of small nuclei and internal myelinated pathways within the basal ganglia, thalamus, brainstem and cerebellum. Contrast was sufficient to visualize the presence and variation of horizontal layers in the cerebral cortex. 3D isotropic resolution datasets facilitated simultaneous multi-planar visualization and efficient production of specific tailored oblique image orientations to improve understanding of complex subcortical anatomy. Conclusions: We created an unlabeled high-resolution digital 3D MRI dataset of neuroanatomy as an online resource for readers to download, manipulate, annotate and use for clinical practice, research and teaching that is complementary to traditional histology-based atlases. Digital MRI contrast is quantifiable, reproducible across brains and could help validate novel MRI strategies for in vivo structure visualization.

Percutaneous cordotomy is well-established as a safe and effective treatment of cancer-associated pain. It remains a first-line treatment in countries where more expensive treatments such as implantable neurostimulators and pumps are not routinely available. We present a case report of a patient with metastatic adenocarcinoma of the esophagus and refractory right upper extremity pain, who was successfully treated via percutaneous CT-guided cordotomy. The procedure was completed in an outpatient setting; the patient was discharged after several hours, with immediate pain relief. He continued to benefit from the procedure for several months until he succumbed to his disease. The technique, decision making, complication profile, as well as the existing experience are presented and discussed in detail.