Evaluation of Gliomas with Magnetic Resonance Fingerprinting with PET Correlation-A Comparative Study.

OBJECTIVES: Advanced MR imaging of brain tumors is still mainly based on qualitative imaging. PET imaging offers additive metabolic information, and MR fingerprinting (MRF) offers a novel approach to quantitative data acquisition. The purpose of this study was to evaluate the ability of MRF to predict tumor regions and grading in combination with PET. METHODS: Seventeen patients with histologically verified infiltrating gliomas and available amino-acid PET data were enrolled. ROIs for solid tumor parts (SPo), perifocal edema (ED1), and normal-appearing white matter (NAWM) were selected on conventional MRI sequences and aligned to the MRF and PET images. The predictability of gliomas by region and grading as well as intermodal correlations were assessed. RESULTS: For MRF, we calculated an overall predictability by region (SPo, ED1, and NAWM) for all of the MRF parameters of 76.5%, 47.1%, and 94.1%, respectively. The overall ability to distinguish low- from high-grade gliomas using MRF was 88.9% for LGG and 75% for HGG, with an accuracy of 82.4%, a ppV of 85.71%, and an npV of 80%. PET positivity was found in 13/17 patients for solid tumor parts, and in 3/17 patients for the edema region. However, there was no significant difference in region-specific MRF values between PET positive and PET negative patients. CONCLUSIONS: MRF and PET provide quantitative measurements of the tumor tissue characteristics of gliomas, with good predictability. Nonetheless, the results are dissimilar, reflecting the different underlying mechanisms of each method.

MR Fingerprinting-A Radiogenomic Marker for Diffuse Gliomas.

(1) Background: Advanced MR imaging (MRI) of brain tumors is mainly based on qualitative contrast images. MR Fingerprinting (MRF) offers a novel approach. The purpose of this study was to use MRF-derived T1 and T2 relaxation maps to differentiate diffuse gliomas according to isocitrate dehydrogenase (IDH) mutation. (2) Methods: Twenty-four patients with histologically verified diffuse gliomas (14 IDH-mutant, four 1p/19q-codeleted, 10 IDH-wildtype) were enrolled. MRF T1 and T2 relaxation times were compared to apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV) within solid tumor, peritumoral edema, and normal-appearing white matter (NAWM), using contrast-enhanced MRI, diffusion-, perfusion-, and susceptibility-weighted imaging. For perfusion imaging, a T2* weighted perfusion sequence with leakage correction was used. Correlations of MRF T1 and T2 times with two established conventional sequences for T1 and T2 mapping were assessed (a fast double inversion recovery-based MR sequence ('MP2RAGE') for T1 quantification and a multi-contrast spin echo-based sequence for T2 quantification). (3) Results: MRF T1 and T2 relaxation times were significantly higher in the IDH-mutant than in IDH-wildtype gliomas within the solid part of the tumor (p = 0.024 for MRF T1, p = 0.041 for MRF T2). MRF T1 and T2 relaxation times were significantly higher in the IDH-wildtype than in IDH-mutant gliomas within peritumoral edema less than or equal to 1cm adjacent to the tumor (p = 0.038 for MRF T1 mean, p = 0.010 for MRF T2 mean). In the solid part of the tumor, there was a high correlation between MRF and conventionally measured T1 and T2 values (r = 0.913, p < 0.001 for T1, r = 0.775, p < 0.001 for T2), as well as between MRF and ADC values (r = 0.813, p < 0.001 for T2, r = 0.697, p < 0.001 for T1). The correlation was weak between the MRF and rCBV values (r = -0.374, p = 0.005 for T2, r = -0.181, p = 0.181 for T1). (4) Conclusions: MRF enables fast, single-sequence based, multi-parametric, quantitative tissue characterization of diffuse gliomas and may have the potential to differentiate IDH-mutant from IDH-wildtype gliomas.

Reproducibility and Repeatability of MR Fingerprinting Relaxometry in the Human Brain.

Background Only sparse literature investigates the reproducibility and repeatability of relaxometry methods in MRI. However, statistical data on reproducibility and repeatability of any quantitative method is essential for clinical application. Purpose To evaluate the reproducibility and repeatability of two-dimensional fast imaging with steady-state free precession MR fingerprinting in vivo in human brains. Materials and Methods Two-dimensional section-selective MR fingerprinting based on a steady-state free precession sequence with an external radiofrequency transmit field, or B1+, correction was used to generate T1 and T2 maps. This prospective study was conducted between July 2017 and January 2018 with 10 scanners from a single manufacturer, including different models, at four different sites. T1 and T2 relaxation times and their variation across scanners (reproducibility) as well as across repetitions on a scanner (repeatability) were analyzed. The relative deviations of T1 and T2 to the average (95% confidence interval) were calculated for several brain compartments. Results Ten healthy volunteers (mean age ± standard deviation, 28.5 years ± 6.9; eight men, two women) participated in this study. Reproducibility and repeatability of T1 and T2 measures in the human brain varied across brain compartments (1.8%-20.9%) and were higher in solid tissues than in the cerebrospinal fluid. T1 measures in solid tissue brain compartments were more stable compared with T2 measures. The half-widths of the confidence intervals for relative deviations were 3.4% for mean T1 and 8.0% for mean T2 values across scanners. Intrascanner repeatability half-widths of the confidence intervals for relative deviations were in the range of 2.0%-3.1% for T1 and 3.1%-7.9% for T2. Conclusion This study provides values on reproducibility and repeatability of T1 and T2 relaxometry measured with fast imaging with steady-state free precession MR fingerprinting in brain tissues of healthy volunteers. Reproducibility and repeatability are considerably higher in solid brain compartments than in cerebrospinal fluid and are higher for T1 than for T2. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Barkhof and Parker in this issue.

High-resolution metabolic mapping of gliomas via patch-based super-resolution magnetic resonance spectroscopic imaging at 7T.

OBJECTIVES: To demonstrate the feasibility of 7 T magnetic resonance spectroscopic imaging (MRSI), combined with patch-based super-resolution (PBSR) reconstruction, for high-resolution multi-metabolite mapping of gliomas. MATERIALS AND METHODS: Ten patients with WHO grade II, III and IV gliomas (6/4, male/female; 45 ±â€¯9 years old) were prospectively measured between 2014 and 2018 on a 7 T whole-body MR imager after routine 3 T magnetic resonance imaging (MRI) and positron emission tomography (PET). Free induction decay MRSI with a 64 × 64-matrix and a nominal voxel size of 3.4 × 3.4 × 8 mm³ was acquired in six minutes, along with standard T1/T2-weighted MRI. Metabolic maps were obtained via spectral LCmodel processing and reconstructed to 0.9 × 0.9 × 8 mm³ resolutions via PBSR. RESULTS: Metabolite maps obtained from combined 7 T MRSI and PBSR resolved the density of metabolic activity in the gliomas in unprecedented detail. Particularly in the more heterogeneous cases (e.g. post resection), metabolite maps enabled the identification of complex metabolic activities, which were in topographic agreement with PET enhancement. CONCLUSIONS: PBSR-MRSI combines the benefits of ultra-high-field MR systems, cutting-edge MRSI, and advanced postprocessing to allow millimetric resolution molecular imaging of glioma tissue beyond standard methods. An ideal example is the accurate imaging of glutamine, which is a prime target of modern therapeutic approaches, made possible due to the higher spectral resolution of 7 T systems.

Key clinical benefits of neuroimaging at 7T.

The growing interest in ultra-high field MRI, with more than 35.000 MR examinations already performed at 7T, is related to improved clinical results with regard to morphological as well as functional and metabolic capabilities. Since the signal-to-noise ratio increases with the field strength of the MR scanner, the most evident application at 7T is to gain higher spatial resolution in the brain compared to 3T. Of specific clinical interest for neuro applications is the cerebral cortex at 7T, for the detection of changes in cortical structure, like the visualization of cortical microinfarcts and cortical plaques in Multiple Sclerosis. In imaging of the hippocampus, even subfields of the internal hippocampal anatomy and pathology may be visualized with excellent spatial resolution. Using Susceptibility Weighted Imaging, the plaque-vessel relationship and iron accumulations in Multiple Sclerosis can be visualized, which may provide a prognostic factor of disease. Vascular imaging is a highly promising field for 7T which is dealt with in a separate dedicated article in this special issue. The static and dynamic blood oxygenation level-dependent contrast also increases with the field strength, which significantly improves the accuracy of pre-surgical evaluation of vital brain areas before tumor removal. Improvement in acquisition and hardware technology have also resulted in an increasing number of MR spectroscopic imaging studies in patients at 7T. More recent parallel imaging and short-TR acquisition approaches have overcome the limitations of scan time and spatial resolution, thereby allowing imaging matrix sizes of up to 128×128. The benefits of these acquisition approaches for investigation of brain tumors and Multiple Sclerosis have been shown recently. Together, these possibilities demonstrate the feasibility and advantages of conducting routine diagnostic imaging and clinical research at 7T.

Seven-Tesla MRI of Hippocampal Sclerosis: An In Vivo Feasibility Study With Histological Correlations.

INTRODUCTION: Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsy in adults. Because approximately half of these patients develop drug resistance, epilepsy surgery designed to remove the epileptogenic zone is an excellent option in selected patients. Histopathological analyses of hippocampal specimens in TLE patients revealed 4 types of Ammon's horn sclerosis, which are correlated with long-term epileptological outcome. The aim of this study was the correlation of noninvasive, high-resolution, morphological magnetic resonance imaging (MRI) at an ultra-high-field (7 T) of the hippocampus in TLE patients with histopathological findings. METHODS: High-resolution, T2-weighted FSE MRI in 14 patients with drug-resistant temporal lobe epilepsy was performed on a 7 T Magnetom using a 32-channel coil. Four independent investigators assessed the delineation and semiquantitative evaluation of volume, signal intensity, internal architecture, and overall grading of the hippocampal subfields CA1-4, as well as the presence of the dentate granule cell layer (DGCL), on MRI scans. Results were compared with semiquantitative evaluation of neuronal loss and astrogliosis in the histological sections of the surgical specimens. RESULTS: Seven-tesla MR examinations were evaluable in 13 cases. Volume loss and signal intensity, as well as overall grading, showed a strong correlation between MRI and histology in individual CA regions. Furthermore, sensitivity and specificity values up to 100% were found for the detection of pathology in the CA subfields. The prediction of Ammon's horn sclerosis type was correct in up to 12 of 13 cases, whereas the dentate gyrus could not be delineated on MRI. DISCUSSION: High-resolution, ultra-high-field MRI is a promising tool for the detection of subtle changes in the hippocampus in patients with temporal lobe epilepsy. Large cohorts will be necessary to confirm the predictive value of 7 T MRI in the preoperative evaluation of TLE patients.

Comparison of Routine Knee Magnetic Resonance Imaging at 3 T and 7 T.

OBJECTIVE: The aim of this study was to compare quantitative and semiquantitative parameters (signal-to-noise ratio [SNR] and diagnostic confidence) from a standard knee magnetic resonance imaging (MRI) examination with comparable sequence protocols and acquisition times at 3 T and at 7 T. MATERIALS AND METHODS: Forty patients experiencing knee pain of unknown etiology underwent comparable MR protocols with standard turbo-spin echo and short tau inversion recovery sequences of the knee joint (5 sequences) at 3 T and 7 T. For quantitative analysis, SNR was determined using these 5 sequences and 3 additional morphological sequences. For a semiquantitative assessment of diagnostic confidence, a diagnostic confidence score (DCS) was assigned, using a 10-point scale. Two experienced radiologists who specialized in musculoskeletal imaging and who were blinded to the field-strength independently assessed 22 potential pathological findings, in total, in 4 anatomically defined areas in the knee joint and rated their diagnostic confidence. RESULTS: In quantitative analysis, all sequences provided higher voxel-volume-adjusted SNR values at 7 T compared with that at 3 T. In semiquantitative analysis, summed DCS values for potential pathological findings in each of the 4 anatomically defined areas were higher at 7 T compared with that at 3 T. There was a statistically significant improvement in the DCS for both readers at 7 T for the diagnosis and exclusion of focal or diffuse grade I or II cartilage defects in the patellar cartilage. For 8 potential pathological findings, a statistically significant difference between the 2 field-strengths could be observed for 1 reader only. For the residual 13 potential pathological findings, there was no statistically significant difference observed. The percentage of concordant ratings was 84.6% at 3 T and 85.4% at 7 T. CONCLUSIONS: Ultra-high-field MRI at 7 T improved the overall diagnostic confidence in routine MRI of the knee joint compared with that at 3 T. This is especially true for small joint structures and subtle lesions. Higher spatial resolution was identified as the main reason for this improvement.

Focal and Generalized Patterns of Cerebral Cortical Veins Due to Non-Convulsive Status Epilepticus or Prolonged Seizure Episode after Convulsive Status Epilepticus - A MRI Study Using Susceptibility Weighted Imaging.

OBJECTIVE: The aim of this study was to investigate variant patterns of cortical venous oxygenation during status epilepticus (SE) using susceptibility-weighted imaging (SWI). METHODS: We analyzed magnetic resonance imaging (MRI) scans of 26 patients with clinically witnessed prolonged seizures and/or EEG-confirmed SE. All MRI exams encompassed SWI, dynamic susceptibility contrast perfusion MRI (MRI-DSC) and diffusion-weighted imaging (DWI). We aimed to identify distinct patterns of SWI signal alterations that revealed regional or global increases of cerebral blood flow (CBF) and DWI restrictions. We hypothesized that SWI-related oxygenation patterns reflect ictal or postictal patterns that resemble SE or sequelae of seizures. RESULTS: Sixteen patients were examined during nonconvulsive status epilepticus (NCSE) as confirmed by EEG, a further ten patients suffered from witnessed and prolonged seizure episode ahead of imaging without initial EEG. MRI patterns of 15 of the 26 patients revealed generalized hyperoxygenation by SWI in keeping with either global or multifocal cortical hyperperfusion. Eight patients revealed a focal hyperoxygenation pattern related to focal CBF increase and three patients showed a focal deoxygenation pattern related to focal CBF decrease. CONCLUSIONS: SWI-related hyper- and deoxygenation patterns resemble ictal and postictal CBF changes within a range from globally increased to focally decreased perfusion. In all 26 patients the SWI patterns were in keeping with ictal hyperperfusion (hyperoxygenation patterns) or postictal hypoperfusion (deoxygenation patterns) respectively. A new finding of this study is that cortical venous patterns in SWI can be not only focally, but globally attenuated. SWI may thus be considered as an alternative contrast-free MR sequence to identify perfusion changes related to ictal or postictal conditions.

Comparison of Routine Brain Imaging at 3 T and 7 T.

OBJECTIVE: The aim of this study was to compare quantitative and semiquantitative parameters (signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], image quality, diagnostic confidence) from a standard brain magnetic resonance imaging examination encompassing common neurological disorders such as demyelinating disease, gliomas, cerebrovascular disease, and epilepsy, with comparable sequence protocols and acquisition times at 3 T and at 7 T. MATERIALS AND METHODS: Ten healthy volunteers and 4 subgroups of 40 patients in total underwent comparable magnetic resonance protocols with standard diffusion-weighted imaging, 2D and 3D turbo spin echo, 2D and 3D gradient echo and susceptibility-weighted imaging of the brain (10 sequences) at 3 T and 7 T. The subgroups comprised patients with either lesional (n = 5) or nonlesional (n = 4) epilepsy, intracerebral tumors (n = 11), demyelinating disease (n = 11) (relapsing-remitting multiple sclerosis [MS, n = 9], secondary progressive MS [n = 1], demyelinating disease not further specified [n = 1]), or chronic cerebrovascular disorders [n = 9]). For quantitative analysis, SNR and CNR were determined. For a semiquantitative assessment of the diagnostic confidence, a 10-point scale diagnostic confidence score (DCS) was applied. Two experienced radiologists with additional qualification in neuroradiology independently assessed, blinded to the field strength, 3 pathology-specific imaging criteria in each of the 4 disease groups and rated their diagnostic confidence. The overall image quality was semiquantitatively assessed using a 4-point scale taking into account whether diagnostic decision making was hampered by artifacts or not. RESULTS: Without correction for spatial resolution, SNR was higher at 3 T except in the T2 SPACE 3D, DWI single shot, and DIR SPACE 3D sequences. The SNR corrected by the ratio of 3 T/7 T voxel sizes was higher at 7 T than at 3 T in 10 of 11 sequences (all except for T1 MP2RAGE 3D).In CNR, there was a wide variation between sequences and patient cohorts, but average CNR values were broadly similar at 3 T and 7 T.DCS values for all 4 pathologic entities were higher at 7 T than at 3 T. The DCS was significantly higher at 7 T for diagnosis and exclusion of cortical lesions in vascular disease. A tendency to higher DCS at 7 T for cortical lesions in MS was observed, and for the depiction of a central vein and iron deposits within MS lesions. Despite motion artifacts, DCS values were higher at 7 T for the diagnosis and exclusion of hippocampal sclerosis in mesial temporal lobe epilepsy (improved detection of the hippocampal subunits). Interrater agreement was 69.7% at 3 T and 93.3% at 7 T. There was no significant difference in the overall image quality score between 3 T and 7 T taking into account whether diagnostic decision making was hampered by artifacts or not. CONCLUSIONS: Ultra-high-field magnetic resonance imaging at 7 T compared with 3 T yielded an improved diagnostic confidence in the most frequently encountered neurologic disorders. Higher spatial resolution and contrast were identified as the main contributory factors.

Focal hemodynamic patterns of status epilepticus detected by susceptibility weighted imaging (SWI).

OBJECTIVE: To investigate pathological findings in the susceptibility weighted imaging (SWI) of patients experiencing convulsive (CSE) or non-convulsive status epilepticus (NCSE) with focal hyperperfusion in the acute setting. METHODS: Twelve patients (six with NCSE confirmed by electroencephalogram (EEG) and six patients with CSE with seizure event clinically diagnosed) underwent MRI in this acute setting (mean time between onset of symptoms and MRI was 3 h 8 min), including SWI, dynamic susceptibility contrast MR imaging (DSC) and diffusion-weighted imaging (DWI). MRI sequences were retrospectively evaluated and compared with EEG findings (10/12 patients), and clinical symptoms. RESULTS: Twelve out of 12 (100 %) patients showed a focal parenchymal area with pseudo-narrowed cortical veins on SWI, associated with focal hyperperfused areas (increased cerebral blood flow (CBF) and mean transit time (MTT) shortening), and cortical DWI restriction in 6/12 patients (50 %). Additionally, these areas were associated with ictal or postical EEG patterns in 8/10 patients (80 %). Most frequent acute clinical findings were aphasia and/or hemiparesis in eight patients, and all of them showed pseudo-narrowed veins in those parenchymal areas responsible for these symptoms. CONCLUSION: In this study series with CSE and NCSE patients, SWI showed focally pseudo-narrowed cortical veins in hyperperfused and ictal parenchymal areas. Therefore, SWI might have the potential to identify an ictal region in CSE/NCSE. KEY POINTS: • The focal ictal brain regions show hyperperfusion in DSC MR-perfusion imaging. • SWI shows focally diminished cortical veins in hyperperfused ictal regions. • SWI has the potential to identify a focal ictal region in CSE/NCSE.