Case report: Exploring chemoradiotherapy-induced leukoencephalopathy with 7T imaging and quantitative susceptibility mapping.

Chemotherapy and radiotherapy are widely used in the treatment of central nervous system tumors and acute lymphocytic leukemia even in the pediatric population. However, such treatments run the risk of a broad spectrum of cognitive and neurological deficits. Even though the correlation with cognitive decline is still not clear, neuroradiological defects linked to white matter injury and vasculopathies may be identified. Thanks to the use of 7T MRI it is possible to better define the vascular pattern of the brain lesions with the added advantage of identifying their characteristics and anatomical localization, which, however, are not evident with a conventional brain scan. Moreover, the use of Quantitative Susceptibility Mapping (QSM) makes it possible to discriminate between calcium deposits on vessels (chemo-radiation-induced) and hemoglobin deposition in radio-induced cavernomas, speculating, as a result, about the pathophysiology of iatrogenic brain damage. We describe the case of a 9 year-old boy with a T-type acute lymphoid leukemia who had previously been treated with polychemotherapy and high-dose RT. To better define the child's neuroradiological pattern, 7T MRI and QSM were performed in addition to conventional imaging examinations. Our case report suggests the potential usefulness of a QSM study to distinguish radio-induced vascular malformations from mineralizing microangiopathy.

Ex-vivo human pancreatic specimen evaluation by 7 Tesla MRI: a prospective radiological-pathological correlation study.

PURPOSE: To compare the characteristics detected by 7Tesla (7 T) MR and the histological composition of ex-vivo specimens from lesions diagnosed at preoperative CT scan as Pancreatic Ductal Adenocarcinoma (PDAC). MATERIALS AND METHODS: Ten pancreatic specimens were examined. The 7 T imaging protocol included both morphologic and quantitative sequences; the latter was acquired by conventional methods and a novel multiparametric method, the magnetic resonance fingerprinting (MRF) sequence. Two radiologists reviewed the images to: (1) evaluate the quality of the morphological and quantitative sequences by assigning an "image consistency score" on a 4-point scale; (2) identify the lesion, recording its characteristics; (3) perform the quantitative analysis on "target lesion" and "non target tissue". Finally, the specimen was analysed by two pathologists. RESULTS: Seven out of 10 lesions were PDAC, 2/10 were biliary carcinomas, whereas one lesion was an ampullary adenocarcinoma. The quality of the morphological sequences was judged "excellent". The "image consistency score" for the conventional quantitative sequences and MRF were 2.8 ± 0.42 and 2.9 ± 0.57; the "overall MR examination score" was 3.5 ± 0.53. A statistical correlation was found between the relaxation time values of conventional and MRF T1-weighted sequences (p < 0.0001), as well as between conventional and MRF fat- and water-fraction maps (p < 0.05). The "target lesion" and "non target tissue" relaxation time values were statistically different according to conventional T1-, T2-weighted, and MRF T1-weighted sequences. CONCLUSIONS: Conventional T1-, T2-weighted sequences and MRF derived relaxometries may be useful in differentiating between tumour and non-target pancreatic tissue. Moreover, the MRF sequence can be used to obtain reliable relaxation time data.

Evaluation of iron overload in nigrosome 1 via quantitative susceptibility mapping as a progression biomarker in prodromal stages of synucleinopathies.

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies, such as Parkinson's disease (PD), which are characterized by the loss of dopaminergic neurons in substantia nigra, associated with abnormal iron load. The assessment of presymptomatic biomarkers predicting the onset of neurodegenerative disorders is critical for monitoring early signs, screening patients for neuroprotective clinical trials and understanding the causal relationship between iron accumulation processes and disease development. Here, we used Quantitative Susceptibility Mapping (QSM) and 7T MRI to quantify iron deposition in Nigrosome 1 (N1) in early PD (ePD) patients, iRBD patients and healthy controls and investigated group differences and correlation with disease progression. We evaluated the radiological appearance of N1 and analyzed its iron content in 35 ePD, 30 iRBD patients and 14 healthy controls via T2*-weighted sequences and susceptibility (χ) maps. N1 regions of interest (ROIs) were manually drawn on control subjects and warped onto a study-specific template to obtain probabilistic N1 ROIs. For each subject the N1 with the highest mean χ was considered for statistical analysis. The appearance of N1 was rated pathological in 45% of iRBD patients. ePD patients showed increased N1 χ compared to iRBD patients and HC but no correlation with disease duration, indicating that iron load remains stable during the early stages of disease progression. Although no difference was reported in iron content between iRBD and HC, N1 χ in the iRBD group increases as the disease evolves. QSM can reveal temporal changes in N1 iron content and its quantification may represent a valuable presymptomatic biomarker to assess neurodegeneration in the prodromal stages of PD.

7-T MRI of explanted liver and ex-vivo pancreatic specimens: prospective study protocol of radiological-pathological correlation feasibility (the EXLIPSE project).

The study focuses on radiological-pathological correlation between imaging of ex vivo samples obtained by a 7-T scanner and histological examination. The specimens will be derived from native explanted cirrhotic livers, liver grafts excluded from donation because of severe steatosis, and primary pancreatic tumours. Magnetic resonance imaging (MRI) examinations will be performed within 24 h from liver or pancreatic lesion surgical removal. The MRI protocol will include morphological sequences, quantitative T1, T2, and fat-, water-fraction maps with Cartesian k-space acquisition, and multiparametric methods based on a transient-state "MRI fingerprinting". Finally, the specimen will be fixed by formalin. Qualitative imaging analysis will be performed by two independent blinded radiologists to assess image consistency score. Quantitative analysis will be performed by drawing regions of interest on different tissue zones to measure T1 and T2 relaxation times as well as fat- and water-fraction. The same tissue areas will be analysed by the pathologists. This study will provide the possibility to improve our knowledge about qualitative and quantitative abdominal imaging assessment at 7 T, by correlating imaging characteristics and the corresponding histological composition of ex vivo specimens, in order to identify imaging biomarkers. Trial registration: ClinicalTrials.gov : 13646. Registered 9 July 2019-retrospectively registered.

Improving fMRI in signal drop-out regions at 7 T by using tailored radio-frequency pulses: application to the ventral occipito-temporal cortex.

OBJECTIVE: Signal drop-off occurs in echo-planar imaging in inferior brain areas due to field gradients from susceptibility differences between air and tissue. Tailored-RF pulses based on a hyperbolic secant (HS) have been shown to partially recover signal at 3 T, but have not been tested at higher fields. MATERIALS AND METHODS: The aim of this study was to compare the performance of an optimized tailored-RF gradient-echo echo-planar imaging (TRF GRE-EPI) sequence with standard GRE-EPI at 7 T, in a passive viewing of faces or objects fMRI paradigm in healthy subjects. RESULTS: Increased temporal-SNR (tSNR) was observed in the middle and inferior temporal lobes and orbitofrontal cortex of all subjects scanned, but elsewhere tSNR decreased relative to the standard acquisition. In the TRF GRE-EPI, increased functional signal was observed in the fusiform, lateral occipital cortex, and occipital pole, regions known to be part of the visual pathway involved in face-object perception. CONCLUSION: This work highlights the potential of TRF approaches at 7 T. Paired with a reversed-gradient distortion correction to compensate for in-plane susceptibility gradients, it provides an improved acquisition strategy for future neurocognitive studies at ultra-high field imaging in areas suffering from static magnetic field inhomogeneities.

Occupational exposure in MR facilities due to movements in the static magnetic field.

PURPOSE: The exposure of operators moving in the static field of magnetic resonance (MR) facilities was assessed through measurements of the magnetic flux density, which is experienced as variable in time because of the movement. Collected data were processed to allow the comparison with most recent and authoritative safety standards. METHODS: Measurements of the experienced magnetic flux density B were performed using a probe worn by volunteers moving in MR environments. A total of 55 datasets were acquired nearby a 1.5 T, 3 T, and 7 T whole body scanners. Three different metrics were applied: the maximum intensity of B, to be compared with 2013/35/EU Directive exposure limit values for static fields; the maximum variation of the vector B on every 3s-interval, for comparison with the ICNIRP-2014 basic restriction aimed at preventing vertigo effects; two weighted-peak indices (for "sensory" and "health" effects: SENS-WP, HLTH-WP), assessing compliance with ICNIRP-2014 and EU Directive recommendations intended to prevent stimulation effects. RESULTS: Peak values of |B| were greater than 2 T in nine of the 55 datasets. All the datasets at 1.5 T and 3 T were compliant with the limit for vertigo effects, whereas six datasets at 7 T turned out to be noncompliant. At 7 T, all 36 datasets were noncompliant for the SENS-WP index and 26 datasets even for the HLTH-WP one. CONCLUSIONS: Results demonstrate that compliance with EU Directive limits for static fields does not guarantee compliance with ICNIRP-2014 reference levels and clearly show that movements in the static field could be the key component of the occupational exposure to EMF in MR facilities.

SAR prediction in adults and children by combining measured B1+ maps and simulations at 7.0 Tesla.

PURPOSE: To predict local and global specific absorption rate (SAR) in individual subjects. MATERIALS AND METHODS: SAR was simulated for a head volume coil for two imaging sequences: axial T1-weighted "zero" time-of-echo (ZTE) sequence, sagittal T2-weighted fluid attenuated inversion recovery (FLAIR). Two head models (one adult, one child) were simulated inside the coil. For 19 adults and 27 children, measured B1 (+) maps were acquired, and global (head) SAR estimated by the system was recorded. We performed t-test between the B1 (+) in models and human subjects. The B1 (+) maps of individual subjects were used to scale the SAR simulated on the models, to predict local and global (head) SAR. A phantom experiment was performed to validate SAR prediction, using a fiberoptic temperature probe to measure the temperature rise due to ZTE scanning. RESULTS: The normalized B1 (+) standard deviation in subjects was not significantly different from that of the models (P > 0.68 and P > 0.54). The rise in temperature generated in the phantom by ZTE was 0.3°C; from the heat equation it followed that the temperature-based measured SAR was 2.74 W/kg, while the predicted value was 3.1 W/kg. CONCLUSION: For ZTE and FLAIR, limits on maximum local and global SAR were met in all subjects, both adults and children. To enhance safety in adults and children with 7.0 Tesla MR systems, we suggest the possibility of using SAR prediction. J. MAGN. RESON. IMAGING 2016;44:1048-1055.

7T MRI in focal epilepsy with unrevealing conventional field strength imaging.

OBJECTIVE: To assess the diagnostic yield of 7T magnetic resonance imaging (MRI) in detecting and characterizing structural lesions in patients with intractable focal epilepsy and unrevealing conventional (1.5 or 3T) MRI. METHODS: We conducted an observational clinical imaging study on 21 patients (17 adults and 4 children) with intractable focal epilepsy, exhibiting clinical and electroencephalographic features consistent with a single seizure-onset zone (SOZ) and unrevealing conventional MRI. Patients were enrolled at two tertiary epilepsy surgery centers and imaged at 7T, including whole brain (three-dimensional [3D] T1 -weighted [T1W] fast-spoiled gradient echo (FSPGR), 3D susceptibility-weighted angiography [SWAN], 3D fluid-attenuated inversion recovery [FLAIR]) and targeted imaging (2D T2*-weighted dual-echo gradient-recalled echo [GRE] and 2D gray-white matter tissue border enhancement [TBE] fast spin echo inversion recovery [FSE-IR]). MRI studies at 1.5 or 3T deemed unrevealing at the referral center were reviewed by three experts in epilepsy imaging. Reviewers were provided information regarding the suspected localization of the SOZ. The same team subsequently reviewed 7T images. Agreement in imaging interpretation was reached through consensus-based discussions based on visual identification of structural abnormalities and their likely correlation with clinical and electrographic data. RESULTS: 7T MRI revealed structural lesions in 6 (29%) of 21 patients. The diagnostic gain in detection was obtained using GRE and FLAIR images. Four of the six patients with abnormal 7T underwent epilepsy surgery. Histopathology revealed focal cortical dysplasia (FCD) in all. In the remaining 15 patients (71%), 7T MRI remained unrevealing; 4 of the patients underwent epilepsy surgery and histopathologic evaluation revealed gliosis. SIGNIFICANCE: 7T MRI improves detection of epileptogenic FCD that is not visible at conventional field strengths. A dedicated protocol including whole brain FLAIR and GRE images at 7T targeted at the suspected SOZ increases the diagnostic yield.

Evaluation of 3D radio-frequency electromagnetic fields for any matching and coupling conditions by the use of basis functions.

A procedure for evaluating radio-frequency electromagnetic fields in anatomical human models for any matching and coupling conditions is introduced. The procedure resorts to the extraction of basis functions: such basis functions, which represent the fields produced by each individual port without any residual coupling, are derived through an algebraic procedure which uses the S parameter matrix and the fields calculated in one (only) full-wave simulation. The basis functions are then used as building-blocks for calculating the fields for any other S parameter matrix. The proposed approach can be used both for volume coil driven in quadrature and for parallel transmission configuration.

Tissue Border Enhancement by inversion recovery MRI at 7.0 Tesla.

INTRODUCTION: This contribution presents a magnetic resonance imaging (MRI) acquisition technique named Tissue Border Enhancement (TBE), whose purpose is to produce images with enhanced visualization of borders between two tissues of interest without any post-processing. METHODS: The technique is based on an inversion recovery sequence that employs an appropriate inversion time to produce images where the interface between two tissues of interest is hypo-intense; therefore, tissue borders are clearly represented by dark lines. This effect is achieved by setting imaging parameters such that two neighboring tissues of interest have magnetization with equal magnitude but opposite sign; therefore, the voxels containing a mixture of each tissue (that is, the tissue interface) possess minimal net signal. The technique was implemented on a 7.0 T MRI system. RESULTS: This approach can assist the definition of tissue borders, such as that between cortical gray matter and white matter; therefore, it could facilitate segmentation procedures, which are often challenging on ultra-high-field systems due to inhomogeneous radiofrequency distribution. TBE allows delineating the contours of structural abnormalities, and its capabilities were demonstrated with patients with focal cortical dysplasia, gray matter heterotopia, and polymicrogyria. CONCLUSION: This technique provides a new type of image contrast and has several possible applications in basic neuroscience, neurogenetic research, and clinical practice, as it could improve the detection power of MRI in the characterization of cortical malformations, enhance the contour of small anatomical structures of interest, and facilitate cortical segmentation.

Proton MR spectroscopy of cerebral gliomas at 3 T: spatial heterogeneity, and tumour grade and extent.

This study aimed to evaluate the usefulness of proton MR spectroscopic imaging ((1)H-MRSI) at 3 T in differentiating high- from low-grade gliomas, and tumour from necrosis, oedema or normal tissue. Forty-four patients with brain gliomas and four with meningiomas were retrospectively reviewed. The normalised metabolites choline (nCho), N-acetylaspartate (nNAA), creatine (nCr) and lactate/lipids (nLL), and the metabolite ratios Cho/NAA, NAA/Cr and Cho/Cr were calculated. Necrotic-appearing areas showed two spectroscopic patterns: "necrosis" with variable nCho and high nLL, and "cystic necrosis" with variable nLL or nonevident peaks. Peri-enhancing oedematous-appearing areas showed three spectroscopic patterns ("tumour" with abnormal Cho/NAA, "oedema" with normal Cho/NAA and "tumour/oedema" with normal nCho and abnormal Cho/NAA) in gliomas, and one ("oedema") in meningiomas. Peri-enhancing or peri-tumour normal-appearing areas showed two patterns ("infiltrated" with abnormal nCho and/or Cho/NAA and "normal" with normal spectra) in gliomas and one ("normal") in meningiomas. Discriminant analysis showed that classification accuracy between high- and low-grade glioma masses was better with normalised metabolites or all parameters together than metabolite ratios and that among peri-enhancing areas was much better with normalised metabolites. The analysis of spatial distribution of normalised metabolites by 3-T (1)H-MRSI helps to discriminate among different tissues, offering information not available with conventional MRI.

Inversion of perceived direction of motion caused by spatial undersampling in two children with periventricular leukomalacia.

We report here two cases of two young diplegic patients with cystic periventricular leukomalacia who systematically, and with high sensitivity, perceive translational motion of a random-dot display in the opposite direction. The apparent inversion was specific for translation motion: Rotation and expansion motion were perceived correctly, with normal sensitivity. It was also specific for random-dot patterns, not occurring with gratings. For the one patient that we were able to test extensively, contrast sensitivity for static stimuli was normal, but was very low for direction discrimination at high spatial frequencies and all temporal frequencies. His optokinetic nystagmus movements were normal but he was unable to track a single translating target, indicating a perceptual origin of the tracking deficit. The severe deficit for motion perception was also evident in the seminatural situation of a driving simulation video game. The perceptual deficit for translational motion was reinforced by functional magnetic resonance imaging studies. Translational motion elicited no response in the MT complex, although it did produce a strong response in many visual areas when contrasted with blank stimuli. However, radial and rotational motion produced a normal pattern of activation in a subregion of the MT complex. These data reinforce the existent evidence for independent cortical processing for translational, and circular or radial flow motion, and further suggest that the two systems have different vulnerability and plasticity to prenatal damage. They also highlight the complexity of visual motion perception, and how the delicate balance of neural activity can lead to paradoxical effects such as consistent misperception of the direction of motion. We advance a possible explanation of a reduced spatial sampling of the motion stimuli and report a simple model that simulates well the experimental results.

Proton MR spectroscopy of the brain at 3 T: an update.

Proton magnetic resonance spectroscopy ((1)H-MRS) provides specific metabolic information not otherwise observable by any other imaging method. (1)H-MRS of the brain at 3 T is a new tool in the modern neuroradiological armamentarium whose main advantages, with respect to the well-established and technologically advanced 1.5-T (1)H-MRS, include a higher signal-to-noise ratio, with a consequent increase in spatial and temporal resolutions, and better spectral resolution. These advantages allow the acquisition of higher quality and more easily quantifiable spectra in smaller voxels and/or in shorter times, and increase the sensitivity in metabolite detection. However, these advantages may be hampered by intrinsic field-dependent technical issues, such as decreased T(2) signal, chemical shift dispersion errors, J-modulation anomalies, increased magnetic susceptibility, eddy current artifacts, challenges in designing and obtaining appropriate radiofrequency coils, magnetic field instability and safety hazards. All these limitations have been tackled by manufacturers and researchers and have received one or more solutions. Furthermore, advanced (1)H-MRS techniques, such as specific spectral editing, fast (1)H-MRS imaging and diffusion tensor (1)H-MRS imaging, have been successfully implemented at 3 T. However, easier and more robust implementations of these techniques are still needed before they can become more widely used and undertake most of the clinical and research (1)H-MRS applications.

Taylor-type focal cortical dysplasia: is the epilepsy always resistant to medical treatment?

Patients with Taylor-type focal cortical dysplasia (TTFCD) generally present with medically intractable epilepsy and impaired neurological and/or intellectual functioning. Surgery usually proves to be the only treatment approach leading to control of seizures. We describe a 17-year-old girl with TTFCD who exhibited a very long period of seizure remission. Combined clinical and neuroimaging findings were compatible with a diagnosis of a balloon cell-subtype TTFCD. As for the clinical course, partial motor seizures began at one year of age and ceased at five: our patient has had no seizure recurrence over a 12-year-follow-up. Moreover, throughout the 15-year follow-up, neurological examinations and cognitive abilities always remained within normal limits. Neuropsychological assessment clearly showed no impairments in executive functions: planning abilities, working memory, attention and impulse control, or constructive aspects of motor coordination. The predominant deficits pertained to verbal abilities in the context of borderline intellectual performances. To our knowledge, this case report documents the longest duration of seizure remission in a patient with TTFCD, thus emphasizing the possible benign course of such dysplastic lesions which usually have a poor prognosis, leading to early surgical treatment.

Multiparametric 3T MR approach to the assessment of cerebral gliomas: tumor extent and malignancy.

INTRODUCTION: Contrast-enhanced MR imaging is the method of choice for routine assessment of brain tumors, but it has limited sensitivity and specificity. We verified if the addition of metabolic, diffusion and hemodynamic information improved the definition of glioma extent and grade. METHODS: Thirty-one patients with cerebral gliomas (21 high- and 10 low-grade) underwent conventional MR imaging, proton MR spectroscopic imaging ((1)H-MRSI), diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) at 3 Tesla, before undergoing surgery and histological confirmation. Normalized metabolite signals, including choline (Cho), N-acetylaspartate (NAA), creatine and lactate/lipids, were obtained by (1)H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI. RESULTS: Perienhancing areas with abnormal MR signal showed 3 multiparametric patterns: "tumor", with abnormal Cho/NAA ratio, lower ADC and higher rCBV; "edema", with normal Cho/NAA ratio, higher ADC and lower rCBV; and "tumor/edema", with abnormal Cho/NAA ratio and intermediate ADC and rCBV. Perienhancing areas with normal MR signal showed 2 multiparametric patterns: "infiltrated", with high Cho and/or abnormal Cho/NAA ratio; and "normal", with normal spectra. Stepwise discriminant analysis showed that the better classification accuracy of perienhancing areas was achieved when regarding all MR variables, while (1)H-MRSI variables and rCBV better differentiated high- from low-grade gliomas. CONCLUSION: Multiparametric MR assessment of gliomas, based on (1)H-MRSI, PWI and DWI, discriminates infiltrating tumor from surrounding vasogenic edema or normal tissues, and high- from low-grade gliomas. This approach may provide useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.

Leukoencephalopathy with bilateral anterior temporal lobe cysts: a further case of this new entity.

The introduction of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy into clinical practice has permitted advances in the definition and categorization of unknown leukodystrophies in children. We report a new type of leukodystrophy, defined by particular MRI and clinical findings, in a child with uneventful pre- and perinatal histories, spasticity, severe mental impairment with absence of language, and deafness. Brain MRI showed lobar white-matter signal abnormalities with extensive cysts in the anterior temporal lobe. The results of all metabolic screening tests, including the specific investigations for leukodystrophy, have been negative. Six years of clinical and MRI-magnetic resonance spectroscopy patient follow-up indicate a nonprogressive clinical and magnetic resonance picture. Owing to the striking similarities with the previous eight patients reported, this additional case supports the identification of a new leukodystrophy.