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• Optimization of a quality control routine across sites in a 3T multicentric study. • More than 80% of ACR quality control measures were within the acceptance ranges. • All measures demonstrated good reproducibility over time. • Inter-vendor differences were observed in the uniformity and geometric metrics. • The automated analysis allows each site to independently monitor scanner performance. Generating big-data is becoming imperative with the advent of machine learning. RIN-Neuroimaging Network addresses this need by developing harmonized protocols for multisite studies to identify quantitative MRI (qMRI) biomarkers for neurological diseases. In this context, image quality control (QC) is essential. Here, we present methods and results of how the RIN performs intra- and inter-site reproducibility of geometrical and image contrast parameters, demonstrating the relevance of such QC practice. American College of Radiology (ACR) large and small phantoms were selected. Eighteen sites were equipped with a 3T scanner that differed by vendor, hardware/software versions, and receiver coils. The standard ACR protocol was optimized (in-plane voxel, post-processing filters, receiver bandwidth) and repeated monthly. Uniformity, ghosting, geometric accuracy, ellipse's ratio, slice thickness, and high-contrast detectability tests were performed using an automatic QC script. Measures were mostly within the ACR tolerance ranges for both T1- and T2-weighted acquisitions, for all scanners, regardless of vendor, coil, and signal transmission chain type. All measurements showed good reproducibility over time. Uniformity and slice thickness failed at some sites. Scanners that upgraded the signal transmission chain showed a decrease in geometric distortion along the slice encoding direction. Inter-vendor differences were observed in uniformity and geometric measurements along the slice encoding direction (i.e. ellipse's ratio). Use of the ACR phantoms highlighted issues that triggered interventions to correct performance at some sites and to improve the longitudinal stability of the scanners. This is relevant for establishing precision levels for future multisite studies of qMRI biomarkers. [ABSTRACT FROM AUTHOR]

[Display omitted] • Reproducibility of harmonized QSM protocol at 3T was tested in a multicentric study. • The traveling brain study yielded optimal structural similarity and reproducibility. • ROI-dependent χ quantification errors were 0.001–0.017 ppm for traveling brains. • In healthy subjects, ROI-dependent χ variability of 0.005–0.025 ppm can be expected. • The harmonized protocol yields reliable χ and it is ready for multicentric studies. Quantitative Susceptibility Mapping (QSM) is an MRI-based technique allowing the non-invasive quantification of iron content and myelination in the brain. The RIN – Neuroimaging Network established an optimized and harmonized protocol for QSM across ten sites with 3T MRI systems from three different vendors to enable multicentric studies. The assessment of the reproducibility of this protocol is crucial to establish susceptibility as a quantitative biomarker. In this work, we evaluated cross-vendor reproducibility in a group of six traveling brains. Then, we recruited fifty-one volunteers and measured the variability of QSM values in a cohort of healthy subjects scanned at different sites, simulating a multicentric study. Both voxelwise and Region of Interest (ROI)-based analysis on cortical and subcortical gray matter were performed. The traveling brain study yielded high structural similarity (∼0.8) and excellent reproducibility comparing maps acquired on scanners from two different vendors. Depending on the ROI, we reported a quantification error ranging from 0.001 to 0.017 ppm for the traveling brains. In the cohort of fifty-one healthy subjects scanned at nine different sites, the ROI-dependent variability of susceptibility values, of the order of 0.005–0.025 ppm, was comparable to the result of the traveling brain experiment. The harmonized QSM protocol of the RIN – Neuroimaging Network provides a reliable quantification of susceptibility in both cortical and subcortical gray matter regions and it is ready for multicentric and longitudinal clinical studies in neurological and pychiatric diseases. [ABSTRACT FROM AUTHOR]

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (− 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of − 3.0 °C. [ABSTRACT FROM AUTHOR]

[Display omitted] • Radiosurgery is a powerful tool in the treatment of a wide spectrum of conditions. • There is a lack of efficient equipment for radiosurgery patient-specific QA programs. • Brain functional treatments condense all the criticalities of radiosurgery dosimetry. • Edgeless diodes are angular independent and measure brain functional treatment dose. • The edgeless diode is an efficient dosimeter for patient-specific QA in radiosurgery. In this work, the potential of an innovative "edgeless" silicon diode was evaluated as a response to the still unmet need of a reliable tool for plan dosimetry verification of very high dose, non-coplanar, patient-specific radiosurgery treatments. In order to prove the effectiveness of the proposed technology, we focused on radiosurgical treatments for functional disease like tremor or pain. The edgeless diodes response has been validated with respect to clinical practice standard detectors by reproducing the reference dosimetry data adopted for the Treatment Planning System. In order to evaluate the potential for radiosurgery patient-specific treatment plan verification, the anthropomorphic phantom Alderson RANDO has been adopted along with three edgeless sensors, one placed in the centre of the Planning Target Volume, one superiorly and one inferiorly. The reference dosimetry data obtained from the edgeless detectors are within 2.6% for output factor, off-axis ratio and well within 2% for tissue phantom ratio when compared to PTW 60,018 diode. The edgeless detectors measure a dose discrepancy of approximately 3.6% from the mean value calculated by the TPS. Larger discrepancies are obtained in very steep gradient dose regions when the sensors are placed outside the PTV. The angular independent edgeless diode is proposed as an innovative dosimeter for patient quality assurance of brain functional disorders and other radiosurgery treatments. The comparison of the diode measurements with TPS calculations confirms that edgeless diodes are suitable candidates for patient-specific dosimetric verification in very high dose ranges delivered by non-isocentric stereotactic radiosurgery modalities. [ABSTRACT FROM AUTHOR]

• Alexander disease can have rapid onset or worsening. • Minor head trauma can be a triggering factor. • The clinical progression might reflect microstructural changes. • Patients with Alexander disease should minimize the risk of head trauma. Alexander disease (ALXDRD) is a rare astrocytic leukodystrophy caused by GFAP mutations. The adult-onset (AO) variant is usually characterized by gradual onset of spastic ataxia and bulbar symptoms with slowly progressive course. We report two AO-ALXDRD cases with rapid worsening after minor head trauma. In one of them, the only post-traumatic neuroimaging change was revealed by diffusion tensor imaging study. Our observations support the link between head trauma and ALXDRD progression, and suggest that this progression may be ascribed to microstructural changes. Clinicians should inform ALXDRD patients to minimize the risk of head trauma. [ABSTRACT FROM AUTHOR]

• Graph-based metrics represent specific topological properties of brain connections. • Multi-site data are essential for evaluating the metrics' reliability. • The results provide useful insights for clinical reliability of topological metrics. The use of topological metrics to derive quantitative descriptors from structural connectomes is receiving increasing attention but deserves specific studies to investigate their reproducibility and variability in the clinical context. This work exploits the harmonization of diffusion-weighted acquisition for neuroimaging data performed by the Italian Neuroscience and Neurorehabilitation Network initiative to obtain normative values of topological metrics and to investigate their reproducibility and variability across centers. Different topological metrics, at global and local level, were calculated on multishell diffusion-weighted data acquired at high-field (e.g. 3 T) Magnetic Resonance Imaging scanners in 13 different centers, following the harmonization of the acquisition protocol, on young and healthy adults. A "traveling brains" dataset acquired on a subgroup of subjects at 3 different centers was also analyzed as reference data. All data were processed following a common processing pipeline that includes data pre-processing, tractography, generation of structural connectomes and calculation of graph-based metrics. The results were evaluated both with statistical analysis of variability and consistency among sites with the traveling brains range. In addition, inter-site reproducibility was assessed in terms of intra-class correlation variability. The results show an inter-center and inter-subject variability of <10%, except for "clustering coefficient" (variability of 30%). Statistical analysis identifies significant differences among sites, as expected given the wide range of scanners' hardware. The results show low variability of connectivity topological metrics across sites running a harmonised protocol. [ABSTRACT FROM AUTHOR]

• Reproducibility of harmonized T1-weighted protocol at 3 T was tested in a multicentric study. • The study measured a global variability that ranges from 11% to 19% for subcortical volumes. • Moreover, we measured a global variability that ranges from 3% to 10% for cortical thicknesses. • The Bland-Altman analysis on traveling brain measures did not detect systematic scanner biases. • SVM can classify the scanner vendor from brain measures with an accuracy = 0.60 ± 0.14 (chance 0.33). Initiatives for the collection of harmonized MRI datasets are growing continuously, opening questions on the reliability of results obtained in multi-site contexts. Here we present the assessment of the brain anatomical variability of MRI-derived measurements obtained from T1-weighted images, acquired according to the Standard Operating Procedures, promoted by the RIN-Neuroimaging Network. A multicentric dataset composed of 77 brain T1w acquisitions of young healthy volunteers (mean age = 29.7 ± 5.0 years), collected in 15 sites with MRI scanners of three different vendors, was considered. Parallelly, a dataset of 7 "traveling" subjects, each undergoing three acquisitions with scanners from different vendors, was also used. Intra-site, intra-vendor, and inter-site variabilities were evaluated in terms of the percentage standard deviation of volumetric and cortical thickness measures. Image quality metrics such as contrast-to-noise and signal-to-noise ratio in gray and white matter were also assessed for all sites and vendors. The results showed a measured global variability that ranges from 11% to 19% for subcortical volumes and from 3% to 10% for cortical thicknesses. Univariate distributions of the normalized volumes of subcortical regions, as well as the distributions of the thickness of cortical parcels appeared to be significantly different among sites in 8 subcortical (out of 17) and 21 cortical (out of 68) regions of i nterest in the multicentric study. The Bland-Altman analysis on "traveling" brain measurements did not detect systematic scanner biases even though a multivariate classification approach was able to classify the scanner vendor from brain measures with an accuracy of 0.60 ± 0.14 (chance level 0.33). [ABSTRACT FROM AUTHOR]

Modern neuroanatomic education should be based on interdisciplinary methods that allow an understanding of the cerebral circuitry, which is at the base of the structural connectivity. Ex-vivo MRI-guided dissection is an essential method for developing and refining the knowledge of complex 3-dimensional brain anatomy and the mutual relationships between structures and architecture of the white matter bundles. The aim of this technical note is to present a new and innovative method of studying human brain white matter. Four adult human cerebral hemispheres were prepared according to the Klinger's method. T1-weighted and T2-weighted and fluid attenuated inversion recovery images were obtained with a 3T magnetic resonance machine. The dissection was performed in a dedicated neurosurgical laboratory equipped with a microscope and an electromagnetic neuronavigation system that guided the whole white matter dissection. Gyri and sulci morphology were studied in detail. The relations between superficial and inner structures were observed before and after the dissection. Gray matter was carefully removed with blunt dissectors, and the U-fibers were exposed. Afterwards, deeper association and projection fibers, such as the arcuate fasciculus, superior and inferior longitudinal fasciculus, corona radiata, extreme and external capsule, claustrum, anterior commissure, and internal capsule were visualized under high magnification. The neuronavigation system was crucial for continuously checking the whole dissection procedure to avoid any accidental excision of fibers. Image-guided neuronavigated dissection can significantly improve the quality of white matter dissection and represents a valid tool for learning the 3-dimensional anatomy of the human brain tracts. [ABSTRACT FROM AUTHOR]

Laser interstitial thermal therapy (LITT) is a minimally invasive ablative technique with specific indications for neuro-oncology, especially in the case of lesions in eloquent areas. Even being performed through a small catheter under stereotactic conditions, the risk of damaging vital structures such as white matter tracts or cortical eloquent areas is not negligible. The mechanism of damage can be related to catheter insertion or to excessive laser ablation. An accurate preoperative workup, aimed at locating the eloquent structures, can be combined with a real-time intraoperative neurophysiologic monitoring to reduce surgical morbidity while maximizing the efficacy of LITT. We developed a synergistic approach for neurophysiology-guided LITT based on state-of-the-art technologies, namely, magnetoencephalography, diffusion tensor imaging, and intraoperative neurophysiologic monitoring. As a result, we improved the planning phase thanks to a more precise representation of functional structures that allows the simulation of different trajectories and the identification of the most suitable trajectory to treat the lesion while respecting the functional boundaries. Catheter insertion is conducted under continuous neurophysiologic feedback and the ablation phase is modeled on the functional boundaries identified by stimulation, allowing it to be extremely accurate. An integrated approached guided by neurophysiology is able to reduce the surgical morbidity even in a relatively accurate technique such as LITT. To the best of our knowledge, this represents the first report on this synergistic approach which could really impact the treatment of tumors in eloquent areas. Future studies are needed in the effort to implement this approach in functional or epilepsy neurosurgery as well. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) is a magnetic resonance modality that permits to characterize the orientation and integrity of white matter (WM). DTI-based tractography techniques, allowing the virtual reconstruction of WM tract pathways, have found wide application in preclinical neurological research. Recently, anatomically detailed rat brain atlases including DTI data were constructed from ex vivo DTI images, but tractographic atlases of normal rats in vivo are still lacking. We propose here a probabilistic tractographic atlas of the main WM tracts in the healthy rat brain based on in vivo DTI acquisition. Our study was carried out on 10 adult female Sprague–Dawley rats using a 7 T preclinical scanner. The MRI protocol permitted a reliable reconstruction of the main rat brain bundles: corpus callosum, cingulum, external capsule, internal capsule, anterior commissure, optic tract. The reconstructed fibers were compared with histological data, proving the viability of in vivo DTI tractography in the rat brain with the proposed acquisition and processing protocol. All the data were registered to a rat brain template in the coordinate system of the commonly used atlas by Paxinos and Watson; then the individual tracts were binarized and averaged, obtaining a probabilistic atlas in Paxinos–Watson space of the main rat brain WM bundles. With respect to the recent high-resolution MRI atlases, the resulting tractographic atlas, available online, provides complementary information about the average anatomical position of the considered WM tracts and their variability between normal animals. Furthermore, reference values for the main DTI-derived parameters, mean diffusivity and fractional anisotropy, were provided. Both these results can be used as references in preclinical studies on pathological rat models involving potential alterations of WM. [ABSTRACT FROM AUTHOR]

Objective Magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) provide noninvasive localization of eloquent brain areas for presurgical planning. The aim of this study is the integration of MEG and fMRI maps into a CyberKnife (CK) system to optimize dose planning. Methods Four patients with brain metastases in the motor area underwent functional imaging study of the hand motor cortex before radiosurgery. MEG data were acquired during a visually cued hand motor task. Motor activations were identified also using an fMRI block-designed paradigm. MEG and fMRI maps were then integrated into a CK system and contoured as organs at risk for treatment planning optimization. Results The integration of fMRI data into the CK system was achieved for all patients by means of a standardized protocol. We also implemented an ad hoc pipeline to convert the MEG signal into a DICOM standard, to make sure that it was readable by our CK treatment planning system. Inclusion of the activation areas into the optimization plan allowed the creation of treatment plans that reduced the irradiation of the motor cortex yet not affecting the brain peripheral dose. Conclusions The availability of advanced neuroimaging techniques is playing an increasingly important role in radiosurgical planning strategy. We successfully imported MEG and fMRI activations into a CK system. This additional information can improve dose sparing of eloquent areas, allowing a more comprehensive investigation of the related dose-volume constraints that in theory could translate into a gain in tumor local control, and a reduction of neurological complications. [ABSTRACT FROM AUTHOR]

The authors report the relevance of Constrained Spherical Deconvolution (CSD)-based tractography in demonstrating and quantitatively assessing a complex midline structure malformation in a 9-year-old girl with moderate intellectual disability and thickening of corpus callosum (CC) body discovered through conventional MRI (cMRI). Color-encoded fractional anisotropy (FA) maps clearly demonstrated what the cMRI showed as a thicknening of CC: a green, longitudinal bundle running dorsally to the body of CC. A more complex midline maldevelopmental disorder was suspected. CSD-based tractography was performed to virtually dissect the anomalous supracallosal longitudinal bundle (SLB), CC, fornix, anterior commissure (AC) and cingula. In addition, DTI-derived metrics were calculated for each virtually dissected fiber tract. The tractography study evidenced projections of the anomalous SLB in left forceps minor and to parietal regions, and projections of the fornix in right forceps minor. CC virtual dissection showed no gross abnormality, and cingula appeared slightly less extended than normal. The considerable thinning of AC hampered its virtual dissection. DTI-derived metrics suggested alterations in fornix microstructure, attributable to higher fiber density. In investigating white matter, cMRI may not be sufficient in addressing and assessing possible anomalies, while advanced CSD-based tractography and DTI-derived metrics may prove helpful in depicting and characterizing white matter anomalies in developmental disorders. [ABSTRACT FROM AUTHOR]