Cross-vendor multiparametric mapping of the human brain using 3D-QALAS: A multicenter and multivendor study.

PURPOSE: To evaluate a vendor-agnostic multiparametric mapping scheme based on 3D quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS) for whole-brain T1, T2, and proton density (PD) mapping. METHODS: This prospective, multi-institutional study was conducted between September 2021 and February 2022 using five different 3T systems from four prominent MRI vendors. The accuracy of this technique was evaluated using a standardized MRI system phantom. Intra-scanner repeatability and inter-vendor reproducibility of T1, T2, and PD values were evaluated in 10 healthy volunteers (6 men; mean age ± SD, 28.0 ± 5.6 y) who underwent scan-rescan sessions on each scanner (total scans = 100). To evaluate the feasibility of 3D-QALAS, nine patients with multiple sclerosis (nine women; mean age ± SD, 48.2 ± 11.5 y) underwent imaging examination on two 3T MRI systems from different manufacturers. RESULTS: Quantitative maps obtained with 3D-QALAS showed high linearity (R2 = 0.998 and 0.998 for T1 and T2, respectively) with respect to reference measurements. The mean intra-scanner coefficients of variation for each scanner and structure ranged from 0.4% to 2.6%. The mean structure-wise test-retest repeatabilities were 1.6%, 1.1%, and 0.7% for T1, T2, and PD, respectively. Overall, high inter-vendor reproducibility was observed for all parameter maps and all structure measurements, including white matter lesions in patients with multiple sclerosis. CONCLUSION: The vendor-agnostic multiparametric mapping technique 3D-QALAS provided reproducible measurements of T1, T2, and PD for human tissues within a typical physiological range using 3T scanners from four different MRI manufacturers.

Noninvasive Magnetic Resonance Imaging Measures of Glymphatic System Activity.

The comprehension of the glymphatic system, a postulated mechanism responsible for the removal of interstitial solutes within the central nervous system (CNS), has witnessed substantial progress recently. While direct measurement techniques involving fluorescence and contrast agent tracers have demonstrated success in animal studies, their application in humans is invasive and presents challenges. Hence, exploring alternative noninvasive approaches that enable glymphatic research in humans is imperative. This review primarily focuses on several noninvasive magnetic resonance imaging (MRI) techniques, encompassing perivascular space (PVS) imaging, diffusion tensor image analysis along the PVS, arterial spin labeling, chemical exchange saturation transfer, and intravoxel incoherent motion. These methodologies provide valuable insights into the dynamics of interstitial fluid, water permeability across the blood-brain barrier, and cerebrospinal fluid flow within the cerebral parenchyma. Furthermore, the review elucidates the underlying concept and clinical applications of these noninvasive MRI techniques, highlighting their strengths and limitations. It addresses concerns about the relationship between glymphatic system activity and pathological alterations, emphasizing the necessity for further studies to establish correlations between noninvasive MRI measurements and pathological findings. Additionally, the challenges associated with conducting multisite studies, such as variability in MRI systems and acquisition parameters, are addressed, with a suggestion for the use of harmonization methods, such as the combined association test (COMBAT), to enhance standardization and statistical power. Current research gaps and future directions in noninvasive MRI techniques for assessing the glymphatic system are discussed, emphasizing the need for larger sample sizes, harmonization studies, and combined approaches. In conclusion, this review provides invaluable insights into the application of noninvasive MRI methods for monitoring glymphatic system activity in the CNS. It highlights their potential in advancing our understanding of the glymphatic system, facilitating clinical applications, and paving the way for future research endeavors in this field. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

Diffusion histogram profiles predict molecular features of grade 4 in histologically lower-grade adult diffuse gliomas following WHO classification 2021.

OBJECTIVES: In the latest World Health Organization classification 2021, grade 4 adult diffuse gliomas can be diagnosed with several molecular features even without histological evidence of necrosis or microvascular proliferation. We aimed to explore whole tumor histogram-derived apparent diffusion coefficient (ADC) histogram profiles for differentiating between the presence (Mol-4) and absence (Mol-2/3) of grade 4 molecular features in histologically lower-grade gliomas. METHODS: Between June 2019 and October 2022, 184 adult patients with diffuse gliomas underwent MRI. After excluding 121 patients, 18 (median age, 64.5 [range, 37-84 years]) Mol-4 and 45 (median 40 [range, 18-73] years) Mol-2/3 patients with histologically lower-grade gliomas were enrolled. Whole tumor volume-of-interest-derived ADC histogram profiles were calculated and compared between the two groups. Stepwise logistic regression analysis with Akaike's information criterion using the ADC histogram profiles with p values < 0.01 and age at diagnosis was used to identify independent variables for predicting the Mol-4 group. RESULTS: The 90th percentile (p < 0.001), median (p < 0.001), mean (p < 0.001), 10th percentile (p = 0.014), and entropy (p < 0.001) of normalized ADC were lower, and kurtosis (p < 0.001) and skewness (p = 0.046) were higher in the Mol-4 group than in the Mol-2/3 group. Multivariate logistic regression analysis revealed that the entropy of normalized ADC and age at diagnosis were independent predictive parameters for the Mol-4 group with an area under the curve of 0.92. CONCLUSION: ADC histogram profiles may be promising preoperative imaging biomarkers to predict molecular grade 4 among histologically lower-grade adult diffuse gliomas. CLINICAL RELEVANCE STATEMENT: This study highlighted the diagnostic usefulness of ADC histogram profiles to differentiate histologically lower grade adult diffuse gliomas with the presence of molecular grade 4 features and those without. KEY POINTS: • ADC histogram profiles to predict molecular CNS WHO grade 4 status among histologically lower-grade adult diffuse gliomas were evaluated. • Entropy of ADC and age were independent predictive parameters for molecular grade 4 status. • ADC histogram analysis is useful for predicting molecular grade 4 among histologically lower-grade gliomas.

Simultaneous relaxometry and morphometry of human brain structures with 3D magnetic resonance fingerprinting: a multicenter, multiplatform, multifield-strength study.

Relaxation times and morphological information are fundamental magnetic resonance imaging-derived metrics of the human brain that reflect the status of the underlying tissue. Magnetic resonance fingerprinting (MRF) enables simultaneous acquisition of T1 and T2 maps inherently aligned to the anatomy, allowing whole-brain relaxometry and morphometry in a single scan. In this study, we revealed the feasibility of 3D MRF for simultaneous brain structure-wise morphometry and relaxometry. Comprehensive test-retest scan analyses using five 1.5-T and three 3.0-T systems from a single vendor including different scanner types across 3 institutions demonstrated that 3D MRF-derived morphological information and relaxation times are highly repeatable at both 1.5 T and 3.0 T. Regional cortical thickness and subcortical volume values showed high agreement and low bias across different field strengths. The ability to acquire a set of regional T1, T2, thickness, and volume measurements of neuroanatomical structures with high repeatability and reproducibility facilitates the ability of longitudinal multicenter imaging studies to quantitatively monitor changes associated with underlying pathologies, disease progression, and treatments.

Amine-weighted chemical exchange saturation transfer magnetic resonance imaging in brain tumors.

Amine-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is particularly valuable as an amine- and pH-sensitive imaging technique in brain tumors, targeting the intrinsically high concentration of amino acids with exchangeable amine protons and reduced extracellular pH in brain tumors. Amine-weighted CEST MRI contrast is dependent on the glioma genotype, likely related to differences in degree of malignancy and metabolic behavior. Amine-weighted CEST MRI may provide complementary value to anatomic imaging in conventional and exploratory therapies in brain tumors, including chemoradiation, antiangiogenic therapies, and immunotherapies. Continual improvement and clinical testing of amine-weighted CEST MRI has the potential to greatly impact patients with brain tumors by understanding vulnerabilities in the tumor microenvironment that may be therapeutically exploited.

Fiber-Specific White Matter Alterations in Parkinson's Disease Patients with GBA Gene Mutations.

BACKGROUND: Patients with Parkinson's disease (PD) carrying GBA gene mutations (GBA-PD) have a more aggressive disease course than those with idiopathic PD (iPD). OBJECTIVE: The objective of this study was to investigate fiber-specific white matter (WM) differences in nonmedicated patients with early-stage GBA-PD and iPD using fixel-based analysis, a novel technique to assess tract-specific WM microstructural and macrostructural features comprehensively. METHODS: Fixel-based metrics, including microstructural fiber density (FD), macrostructural fiber-bundle cross section (FC), and a combination of FD and FC (FDC), were compared among 30 healthy control subjects, 16 patients with GBA-PD, and 35 patients with iPD. Associations between FDC and clinical evaluations were also explored using multiple linear regression analyses. RESULTS: Patients with GBA-PD showed significantly lower FD in the fornix and superior longitudinal fasciculus than healthy control subjects, and lower FC in the corticospinal tract (CST) and lower FDC in the CST, middle cerebellar peduncle, and striatal-thalamo-cortical pathways than patients with iPD. Contrarily, patients with iPD showed significantly higher FC and FDC in the CST and striatal-thalamo-cortical pathways than healthy control subjects. In addition, lower FDC in patients with GBA-PD was associated with reduced glucocerebrosidase enzyme activity, lower cerebrospinal fluid total α-synuclein levels, lower Montreal Cognitive Assessment scores, lower striatal binding ratio, and higher Unified Parkinson's Disease Rating Scale Part III scores. CONCLUSIONS: We report reduced fiber-specific WM density and bundle cross-sectional size in patients with GBA-PD, suggesting neurodegeneration linked to glucocerebrosidase deficiency, α-synuclein accumulation, and poorer cognition and motor functions. Conversely, patients with iPD showed increased fiber bundle size, likely because of WM reorganization. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Deep Learning-Driven Transformation: A Novel Approach for Mitigating Batch Effects in Diffusion MRI Beyond Traditional Harmonization.

BACKGROUND: "Batch effect" in MR images, due to vendor-specific features, MR machine generations, and imaging parameters, challenges image quality and hinders deep learning (DL) model generalizability. PURPOSE: We aim to develop a DL model using contrast adjustment and super-resolution to reduce diffusion-weighted images (DWIs) diversity across magnetic field strengths and imaging parameters. STUDY TYPE: Retrospective. SUBJECTS: The DL model was built using an open dataset from one individual. The MR machine identification model was trained and validated on a dataset of 1134 adults (54% females, 46% males), with 1050 subjects showing no DWI abnormalities and 84 with conditions like stroke and tumors. The 21,000 images were divided into 80% for training, 20% for validation, and 3500 for testing. FIELD STRENGTH/SEQUENCE: Seven MR scanners from four manufacturers with 1.5 T and 3 T magnetic field strengths. DWIs were acquired using spin-echo sequences and high-resolution T2WIs using the T2-SPACE sequence. ASSESSMENT: An experienced, board-certified radiologist evaluated the effectiveness of restoring high-resolution T2WI and harmonizing diverse DWI with metrics such as PSNR and SSIM, and the texture and frequency attributes were further analyzed using gray-level co-occurrence matrix and 1-dimensional power spectral density. The model's impact on machine-specific characteristics was gauged through the performance metrics of a ResNet-50 model. Comprehensive statistical tests were employed for statistical robustness, including McNemar's test and the Dice index. RESULTS: Our DL protocol reduced DWI contrast and resolution variation. ResNet-50 model's accuracy decreased from 0.9443 to 0.5786, precision from 0.9442 to 0.6494, recall from 0.9443 to 0.5786, and F1 score from 0.9438 to 0.5587. The t-SNE visualization indicated more consistent image features across multiple MR devices. Autoencoder halved learning iterations; Dice coefficient >0.74 confirmed signal reproducibility in 84 lesions. CONCLUSION: This study presents a DL strategy to mitigate batch effects in diffusion MR images, improving their quality and generalizability. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Multi-nuclear sodium, diffusion, and perfusion MRI in human gliomas.

PURPOSE: There is limited knowledge about the associations between sodium and proton MRI measurements in brain tumors. The purpose of this study was to quantify intra- and intertumoral correlations between sodium, diffusion, and perfusion MRI in human gliomas. METHODS: Twenty glioma patients were prospectively studied on a 3T MRI system with multinuclear capabilities. Three mutually exclusive tumor volumes of interest (VOIs) were segmented: contrast-enhancing tumor (CET), T2/FLAIR hyperintense non-enhancing tumor (NET), and necrosis. Median and voxel-wise associations between apparent diffusion coefficient (ADC), normalized relative cerebral blood volume (nrCBV), and normalized sodium measurements were quantified for each VOI. RESULTS: Both relative sodium concentration and ADC were significantly higher in areas of necrosis compared to NET (P = 0.003 and P = 0.008, respectively) and CET (P = 0.02 and P = 0.02). Sodium concentration was higher in CET compared to NET (P = 0.04). Sodium and ADC were higher in treated compared to treatment-naïve gliomas within NET (P = 0.006 and P = 0.01, respectively), and ADC was elevated in CET (P = 0.03). Median ADC and sodium concentration were positively correlated across patients in NET (r = 0.77, P < 0.0001) and CET (r = 0.84, P < 0.0001), but not in areas of necrosis (r = 0.45, P = 0.12). Median nrCBV and sodium concentration were negatively correlated across patients in areas of NET (r=-0.63, P = 0.003). Similar associations were observed when examining voxel-wise correlations within VOIs. CONCLUSION: Sodium MRI is positively correlated with proton diffusion MRI measurements in gliomas, likely reflecting extracellular water. Unique areas of multinuclear MRI contrast may be useful in future studies to understand the chemistry of the tumor microenvironment.

Simultaneous quantification of perfusion, permeability, and leakage effects in brain gliomas using dynamic spin-and-gradient-echo echoplanar imaging MRI.

OBJECTIVE: To determine the feasibility and biologic correlations of dynamic susceptibility contrast (DSC), dynamic contrast enhanced (DCE), and quantitative maps derived from contrast leakage effects obtained simultaneously in gliomas using dynamic spin-and-gradient-echo echoplanar imaging (dynamic SAGE-EPI) during a single contrast injection. MATERIALS AND METHODS: Thirty-eight patients with enhancing brain gliomas were prospectively imaged with dynamic SAGE-EPI, which was processed to compute traditional DSC metrics (normalized relative cerebral blood flow [nrCBV], percentage of signal recovery [PSR]), DCE metrics (volume transfer constant [Ktrans], extravascular compartment [ve]), and leakage effect metrics: ΔR2,ss* (reflecting T2*-leakage effects), ΔR1,ss (reflecting T1-leakage effects), and the transverse relaxivity at tracer equilibrium (TRATE, reflecting the balance between ΔR2,ss* and ΔR1,ss). These metrics were compared between patient subgroups (treatment-naïve [TN] vs recurrent [R]) and biological features (IDH status, Ki67 expression). RESULTS: In IDH wild-type gliomas (IDHwt-i.e., glioblastomas), previous exposure to treatment determined lower TRATE (p = 0.002), as well as higher PSR (p = 0.006), Ktrans (p = 0.17), ΔR1,ss (p = 0.035), ve (p = 0.006), and ADC (p = 0.016). In IDH-mutant gliomas (IDHm), previous treatment determined higher Ktrans and ΔR1,ss (p = 0.026). In TN-gliomas, dynamic SAGE-EPI metrics tended to be influenced by IDH status (p ranging 0.09-0.14). TRATE values above 142 mM-1s-1 were exclusively seen in TN-IDHwt, and, in TN-gliomas, this cutoff had 89% sensitivity and 80% specificity as a predictor of Ki67 > 10%. CONCLUSIONS: Dynamic SAGE-EPI enables simultaneous quantification of brain tumor perfusion and permeability, as well as mapping of novel metrics related to cytoarchitecture (TRATE) and blood-brain barrier disruption (ΔR1,ss), with a single contrast injection. CLINICAL RELEVANCE STATEMENT: Simultaneous DSC and DCE analysis with dynamic SAGE-EPI reduces scanning time and contrast dose, respectively alleviating concerns about imaging protocol length and gadolinium adverse effects and accumulation, while providing novel leakage effect metrics reflecting blood-brain barrier disruption and tumor tissue cytoarchitecture. KEY POINTS: • Traditionally, perfusion and permeability imaging for brain tumors requires two separate contrast injections and acquisitions. • Dynamic spin-and-gradient-echo echoplanar imaging enables simultaneous perfusion and permeability imaging. • Dynamic spin-and-gradient-echo echoplanar imaging provides new image contrasts reflecting blood-brain barrier disruption and cytoarchitecture characteristics.

A multi-reader comparison of normal-appearing white matter normalization techniques for perfusion and diffusion MRI in brain tumors.

PURPOSE: There remains no consensus normal-appearing white matter (NAWM) normalization method to compute normalized relative cerebral blood volume (nrCBV) and apparent diffusion coefficient (nADC) in brain tumors. This reader study explored nrCBV and nADC differences using different NAWM normalization methods. METHODS: Thirty-five newly diagnosed glioma patients were studied. For each patient, two readers created four NAWM regions of interests: (1) a single plane in the centrum semiovale (CSOp), (2) 3 spheres in the centrum semiovale (CSOs), (3) a single plane in the slice of the tumor center (TUMp), and (4) 3 spheres in the slice of the tumor center (TUMs). Readers repeated NAWM segmentations 1 month later. Differences in nrCBV and nADC of the FLAIR hyperintense tumor, inter-/intra-reader variability, and time to segment NAWM were assessed. As a validation step, the diagnostic performance of each method for IDH-status prediction was evaluated. RESULTS: Both readers obtained significantly different nrCBV (P < .001), nADC (P < .001), and time to segment NAWM (P < .001) between the four normalization methods. nrCBV and nADC were significantly different between CSO and TUM methods, but not between planar and spherical methods in the same NAWM region. Broadly, CSO methods were quicker than TUM methods, and spherical methods were quicker than planar methods. For all normalization techniques, inter-reader reproducibility and intra-reader repeatability were excellent (intraclass correlation coefficient > 0.9), and the IDH-status predictive performance remained similar. CONCLUSION: The selected NAWM region significantly impacts nrCBV and nADC values. CSO methods, particularly CSOs, may be preferred because of time reduction, similar reader variability, and similar diagnostic performance compared to TUM methods.

Analysis of synthetic magnetic resonance images by multi-channel segmentation increases accuracy of volumetry in the putamen and decreases mis-segmentation in the dural sinuses.

BACKGROUND: Voxel-based morphometry (VBM) using magnetic resonance imaging (MR) has been used to estimate cortical atrophy associated with various diseases. However, there are mis-segmentations of segmented gray matter image in VBM. PURPOSE: To study a twofold evaluation of single- and multi-channel segmentation using synthetic MR images: (1) mis-segmentation of segmented gray matter images in transverse and cavernous sinuses; and (2) accuracy and repeatability of segmented gray matter images. MATERIAL AND METHODS: A total of 13 healthy individuals were scanned with 3D quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS) sequence on a 1.5-T scanner. Three of the 13 healthy participants were scanned five consecutive times for evaluation of repeatability. We used SyMRI software to create images with three contrasts: T1-weighted (T1W), T2-weighted (T2W), and proton density-weighted (PDW) images. Manual regions of interest (ROI) on T1W imaging were individually set as the gold standard in the transverse sinus, cavernous sinus, and putamen. Single-channel (T1W) and multi-channel (T1W + T2W, T1W + PDW, and T1W + T2W + PDW imaging) segmentations were performed with statistical parametric mapping 12 software. RESULTS: We found that mis-segmentations in both the transverse and cavernous sinuses were large in single-channel segmentation compared with multi-channel segmentations. Furthermore, the accuracy of segmented gray matter images in the putamen was high in both multi-channel T1W + PDW and T1W + T2W + PDW segmentations compared with other segmentations. Finally, the highest repeatability of left putamen volumetry was found with multi-channel segmentation T1WI + PDWI. CONCLUSION: Multi-channel segmentation with T1WI + PDWI provides good results for VBM compared with single-channel and other multi-channel segmentations.

Rigid real-time prospective motion-corrected three-dimensional multiparametric mapping of the human brain.

PURPOSE: To develop a rigid real-time prospective motion-corrected multiparametric mapping technique and to test the performance of quantitative estimates. METHODS: Motion tracking and correction were performed by integrating single-shot spiral navigators into a multiparametric imaging technique, three-dimensional quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS). The spiral navigator was optimized, and quantitative measurements were validated using a standard system phantom. The effect of motion correction on whole-brain T1 and T2 mapping under different types of head motion during the scan was evaluated in 10 healthy volunteers. Finally, six patients with Parkinson's disease, which is known to be associated with a high prevalence of motion artifacts, were scanned to evaluate the effectiveness of our method in the real world. RESULTS: The phantom study demonstrated that the proposed motion correction method did not introduce quantitative bias. Improved parametric map quality and repeatability were shown in volunteer experiments with both in-plane and through-plane motions, comparable to the no-motion ground truth. In real-life validation in patients, the approach showed improved parametric map quality compared to images obtained without motion correction. CONCLUSIONS: Real-time prospective motion-corrected multiparametric relaxometry based on 3D-QALAS provided robust and repeatable whole-brain multiparametric mapping.

Multimodal magnetic resonance imaging quantification of gray matter alterations in relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorder.

Herein, we combined neurite orientation dispersion and density imaging (NODDI) and synthetic magnetic resonance imaging (SyMRI) to evaluate the spatial distribution and extent of gray matter (GM) microstructural alterations in patients with relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD). The NODDI (neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISOVF]) and SyMRI (myelin volume fraction [MVF]) measures were compared between age- and sex-matched groups of 30 patients with RRMS (6 males and 24 females; mean age, 51.43 ± 8.02 years), 18 patients with anti-aquaporin-4 antibody-positive NMOSD (2 males and 16 females; mean age, 52.67 ± 16.07 years), and 19 healthy controls (6 males and 13 females; mean age, 51.47 ± 9.25 years) using GM-based spatial statistical analysis. Patients with RRMS showed reduced NDI and MVF and increased ODI and ISOVF, predominantly in the limbic and paralimbic regions, when compared with healthy controls, while only increases in ODI and ISOVF were observed when compared with NMOSD. Compared to NDI and MVF, the changes in ODI and ISOVF were observed more widely, including in the cerebellar cortex. These abnormalities were associated with disease progression and disability. In contrast, patients with NMOSD only showed reduced NDI mainly in the cerebellar, limbic, and paralimbic cortices when compared with healthy controls and patients with RRMS. Taken together, our study supports the notion that GM pathologies in RRMS are distinct from those of NMOSD. However, owing to the limitations of the study, the results should be cautiously interpreted.

Relapse patterns and radiation dose exposure in IDH wild-type glioblastoma at first radiographic recurrence following chemoradiation.

PURPOSE: To quantify the radiation dose distribution and lesion morphometry (shape) at baseline, prior to chemoradiation, and at the time of radiographic recurrence in patients with glioblastoma (GBM). METHODS: The IMRT dose distribution, location of the center of mass, sphericity, and solidity of the contrast enhancing tumor at baseline and the time of tumor recurrence was quantified in 48 IDH wild-type GBM who underwent postoperative IMRT (2 Gy daily for total of 60 Gy) with concomitant and adjuvant temozolomide. RESULTS: Average radiation dose within enhancing tumor at baseline and recurrence was ≥ 60 Gy. Centroid location of the enhancing tumor shifted an average of 11.3 mm at the time of recurrence with respect to pre-IMRT location. A positive correlation was observed between change in centroid location and PFS in MGMT methylated patients (P = 0.0007) and Cox multivariate regression confirmed centroid distance from baseline was associated with PFS when accounting for clinical factors (P = 0.0189). Lesion solidity was higher at recurrence compared to baseline (P = 0.0118). Tumors that progressed > 12 weeks after IMRT were significantly more spherical (P = 0.0094). CONCLUSION: Most GBMs recur local within therapeutic IMRT doses; however, tumors with longer PFS occurred further from the original tumor location and were more solid and/or nodular.

Incidence, molecular characteristics, and imaging features of "clinically-defined pseudoprogression" in newly diagnosed glioblastoma treated with chemoradiation.

PURPOSE: Pseudoprogression (PsP) remains an elusive and clinically important, yet ill-defined, phenomena that, generally, involves a period of early radiographic progression (enhancement) followed by a period of radiographic stability or regression. In the current study, we utilized data from the control arm of a phase III clinical trial in newly-diagnosed glioblastoma to explore imaging characteristics of "clinically-defined PsP", or early radiographic progression (PFS < 6 months from chemoradiation) followed by a long post-progression residual overall survival (ROS > 12 months). METHODS: One hundred sixty-nine patients with newly-diagnosed GBM from the control arm of the AVAglio trial (NCT00943826) who presented with early radiographic progressive disease (PD) (< 6 months) were included. Clinical characteristics, topographical patterns, and radiomic features were compared between newly-diagnosed GBM exhibiting early PD and early death (< 12-month ROS, "true PD") with those exhibiting early PD and a long residual survival (> 12-month ROS, "clinically-defined PsP"). RESULTS: "Clinically-defined PsP" occurred to 38.5% of patients with early PD, and was more associated with MGMT methylation (P = 0.02), younger age (P = 0.003), better neurological performance (P = 0.01), and lower contrast-enhancing tumor volume (P = 0.002) at baseline. GBM showing "true PD" occurred more frequently in the right internal capsule, thalamus, lentiform nucleus, and temporal lobe than those with "clinical PsP". Radiomic analysis predicted "clinical PsP" with > 70% accuracy on the validation dataset. CONCLUSION: Patients with early PD that eventually exhibit "clinically-defined PsP" have distinct clinical, molecular, and MRI characteristics. This information may be useful for treating clinicians to better understand the potential risks and outcome in patients exhibiting early radiographic changes following chemoradiation.

Radiomics with 3-dimensional magnetic resonance fingerprinting: influence of dictionary design on repeatability and reproducibility of radiomic features.

OBJECTIVES: We aimed to investigate the influence of magnetic resonance fingerprinting (MRF) dictionary design on radiomic features using in vivo human brain scans. METHODS: Scan-rescans of three-dimensional MRF and conventional T1-weighted imaging were performed on 21 healthy volunteers (9 males and 12 females; mean age, 41.3 ± 14.6 years; age range, 22-72 years). Five patients with multiple sclerosis (3 males and 2 females; mean age, 41.2 ± 7.3 years; age range, 32-53 years) were also included. MRF data were reconstructed using various dictionaries with different step sizes. First- and second-order radiomic features were extracted from each dataset. Intra-dictionary repeatability and inter-dictionary reproducibility were evaluated using intraclass correlation coefficients (ICCs). Features with ICCs > 0.90 were considered acceptable. Relative changes were calculated to assess inter-dictionary biases. RESULTS: The overall scan-rescan ICCs of MRF-based radiomics ranged from 0.86 to 0.95, depending on dictionary step size. No significant differences were observed in the overall scan-rescan repeatability of MRF-based radiomic features and conventional T1-weighted imaging (p = 1.00). Intra-dictionary repeatability was insensitive to dictionary step size differences. MRF-based radiomic features varied among dictionaries (overall ICC for inter-dictionary reproducibility, 0.62-0.99), especially when step sizes were large. First-order and gray level co-occurrence matrix features were the most reproducible feature classes among different step size dictionaries. T1 map-derived radiomic features provided higher repeatability and reproducibility among dictionaries than those obtained with T2 maps. CONCLUSION: MRF-based radiomic features are highly repeatable in various dictionary step sizes. Caution is warranted when performing MRF-based radiomics using datasets containing maps generated from different dictionaries. KEY POINTS: • MRF-based radiomic features are highly repeatable in various dictionary step sizes. • Use of different MRF dictionaries may result in variable radiomic features, even when the same MRF acquisition data are used. • Caution is needed when performing radiomic analysis using data reconstructed from different dictionaries.

Localization of the central sulcus using the distinctive high signal intensity of the paracentral lobule on T1-weighted images.

PURPOSE: The central sulcus is an important landmark in the brain. This study aimed to investigate the distinctive signal of the paracentral lobule (PL) on T1-weighted images (T1WIs; the white PL sign) and evaluate its usefulness as a new method of identifying the central sulcus. METHODS: T1WIs of the brain of 96 participants (age, 58.9 ± 17.9 years; range, 8-87 years) scanned at 3-T MR system were retrospectively reviewed. First, we qualitatively analyzed the signal of the cortex of the PL by comparing it with that of the ipsilateral superior frontal gyrus on a 4-point grading score. Second, we compared the cortical signal intensity and gray/white-matter contrast between the PL and superior frontal gyrus. Third, we evaluated the usefulness of the PL signal for identifying the central sulcus. RESULTS: The PL cortex was either mildly hyperintense (grade 2) or definitely hyperintense (grade 3) in comparison with that of superior frontal cortex in all participants. The signal intensity of the PL cortex was significantly higher than that of the superior frontal cortex (p < 0.001), whereas the gray/white-matter contrast of the PL was weaker than that of the superior frontal gyrus (p < 0.001). The central sulci were identified with 94.3% accuracy (181/192) using the new method. CONCLUSION: The white PL sign may be helpful in identifying the central sulcus, and this approach can be recognized as a new method for identification of the central sulcus.

Multiple sclerosis plaques may undergo continuous myelin degradation: a cross-sectional study with myelin and axon-related quantitative magnetic resonance imaging metrics.

PURPOSE: We hypothesize that myelin is more susceptible to damage over time than axons. We investigated the association between the estimated duration from the onset of multiple sclerosis (MS) plaques and myelin- and axon-related quantitative synthetic magnetic resonance imaging (SyMRI) and neurite orientation dispersion and density imaging (NODDI) metrics. METHODS: We analyzed 31 patients with MS with 73 newly appeared plaques. Simple linear regression analysis was performed to assess the association between the estimated duration from the onset of plaques and quantitative MRI metrics. These metrics included the myelin volume fraction (MVF), axon volume fraction, and g-ratio in plaque and normal-appearing white matter. RESULTS: MS plaques with a longer estimated duration from onset were significantly correlated with a lower MVF (slope = - 0.0070, R2 = 0.0970), higher g-ratio (slope = 0.0078, R2 = 0.0842) (all P values < 0.05). CONCLUSION: These results suggested that myelin in plaques undergoes continuous damage, more so than axons. Myelin imaging with SyMRI and NODDI may be useful for the quantitative assessment of temporal changes in MS plaques.

Repeatability and reproducibility of human brain morphometry using three-dimensional magnetic resonance fingerprinting.

Three-dimensional (3D) Magnetic resonance fingerprinting (MRF) permits whole-brain volumetric quantification of T1 and T2 relaxation values, potentially replacing conventional T1-weighted structural imaging for common brain imaging analysis. The aim of this study was to evaluate the repeatability and reproducibility of 3D MRF in evaluating brain cortical thickness and subcortical volumetric analysis in healthy volunteers using conventional 3D T1-weighted images as a reference standard. Scan-rescan tests of both 3D MRF and conventional 3D fast spoiled gradient recalled echo (FSPGR) were performed. For each sequence, the regional cortical thickness and volume of the subcortical structures were measured using standard automatic brain segmentation software. Repeatability and reproducibility were assessed using the within-subject coefficient of variation (wCV), intraclass correlation coefficient (ICC), and mean percent difference and ICC, respectively. The wCV and ICC of cortical thickness were similar across all regions with both 3D MRF and FSPGR. The percent relative difference in cortical thickness between 3D MRF and FSPGR across all regions was 8.0 ± 3.2%. The wCV and ICC of the volume of subcortical structures across all structures were similar between 3D MRF and FSPGR. The percent relative difference in the volume of subcortical structures between 3D MRF and FSPGR across all structures was 7.1 ± 3.6%. 3D MRF measurements of human brain cortical thickness and subcortical volumes are highly repeatable, and consistent with measurements taken on conventional 3D T1-weighted images. A slight, consistent bias was evident between the two, and thus careful attention is required when combining data from MRF and conventional acquisitions.

Connectome analysis of male world-class gymnasts using probabilistic multishell, multitissue constrained spherical deconvolution tracking.

In athletes, long-term intensive training has been shown to increase unparalleled athletic ability and might induce brain plasticity. We evaluated the structural connectome of world-class gymnasts (WCGs), as mapped by diffusion-weighted magnetic resonance imaging probabilistic tractography and a multishell, multitissue constrained spherical deconvolution method to increase the precision of tractography at the tissue interfaces. The connectome was mapped in 10 Japanese male WCGs and in 10 age-matched male controls. Network-based statistic identified subnetworks with increased connectivity density in WCGs, involving the sensorimotor, default mode, attentional, visual, and limbic areas. It also revealed a significant association between the structural connectivity of some brain structures with functions closely related to the gymnastic skills and the D-score, which is used as an index of the gymnasts' specific physical abilities for each apparatus. Furthermore, graph theory analysis demonstrated the characteristics of brain anatomical topology in the WCGs. They displayed significantly increased global connectivity strength with decreased characteristic path length at the global level and higher nodal strength and degree in the sensorimotor, default mode, attention, and limbic/subcortical areas at the local level as compared with controls. Together, these findings extend the current understanding of neural mechanisms that distinguish WCGs from controls and suggest brain anatomical network plasticity in WCGs resulting from long-term intensive training. Future studies should assess the contribution of genetic or early-life environmental factors in the brain network organization of WCGs. Furthermore, the indices of brain topology (i.e., connection density and graph theory indices) could become markers for the objective evaluation of gymnastic performance.