Advanced MRI Methods Research Articles

Prevalence of steatotic liver disease, advanced fibrosis and cirrhosis among community-dwelling overweight and obese individuals in the USA

BackgroundThere are limited prospective data among overweight and obese individuals on the prevalence of advanced fibrosis, and cirrhosis using advanced MRI-based methods in the USA. The aim of this study...

Improving advanced intraoperative MRI methods during pediatric neurosurgery.

Advanced intraoperative MR images (ioMRI) acquired during the resection of pediatric brain tumors could offer additional physiological information to preserve healthy tissue. With this work, we aimed to develop a protocol for ioMRI with increased sensitivity for arterial spin labeling (ASL) and diffusion MRI (dMRI), optimized for patient positioning regularly used in the pediatric neurosurgery setting. For ethical reasons, ASL images were acquired in healthy adult subjects that were imaged in the prone and supine position. After this, the ASL cerebral blood flow (CBF) was quantified and compared between both positions. To evaluate the impact of the RF coils setups on image quality, we compared different setups (two vs. four RF coils) by looking at T1-weighted (T1w) signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), as well as undertaking a qualitative evaluation of T1w, T2w, ASL, and dMR images. Mean ASL CBF did not differ between the surgical prone and supine positions in any of the investigated regions of interest or the whole brain. T1w SNR (gray matter: p = 0.016, 34% increase; white matter: p = 0.016, 32% increase) and CNR were higher (p = 0.016) in the four versus two RF coils setups (18.0± 1.8 vs. 13.9± 1.8). Qualitative evaluation of T1w, T2w, ASL, and dMR images resulted in acceptable to good image quality and did not differ statistically significantly between setups. Only the nonweighted diffusion image maps and corticospinal tract reconstructions yielded higher image quality and reduced susceptibility artifacts with four RF coils. Advanced ioMRI metrics were more precise with four RF coils as the standard deviation decreased. Taken together, we have investigated the practical use of advanced ioMRI during pediatric neurosurgery. We conclude that ASL CBF quantification in the surgical prone position is valid and that ASL and dMRI acquisition with two RF coils can be performed adequately for clinical use. With four versus two RF coils, the SNR of the images increases, and the sensitivity to artifacts reduces.

Novel pore size-controlled, susceptibility matched, 3D-printed MRI phantoms.

We report the design concept and fabrication of MRI phantoms, containing blocks of aligned microcapillaires that can be stacked into larger arrays to construct diameter distribution phantoms or fractured, to create a "powder-averaged" emulsion of randomly oriented blocks for vetting or calibrating advanced MRI methods, that is, diffusion tensor imaging, AxCaliber MRI, MAP-MRI, and multiple pulsed field gradient or double diffusion-encoded microstructure imaging methods. The goal was to create a susceptibility-matched microscopically anisotropic but macroscopically isotropic phantom with a ground truth diameter that could be used to vet advanced diffusion methods for diameter determination in fibrous tissues. Two-photon polymerization, a novel three-dimensional printing method is used to fabricate blocks of capillaries. Double diffusion encoding methods were employed and analyzed to estimate the expected MRI diameter. Susceptibility-matched microcapillary blocks or modules that can be assembled into large-scale MRI phantoms have been fabricated and measured using advanced diffusion methods, resulting in microscopic anisotropy and random orientation. This phantom can vet and calibrate various advanced MRI methods and multiple pulsed field gradient or diffusion-encoded microstructure imaging methods. We demonstrated that two double diffusion encoding methods underestimated the ground truth diameter.

Probing Brain Magnetic Susceptibility Alterations in a Mouse Model of Multiple Sclerosis

Multiple sclerosis (MS) is an increasing cause of disability in the United States, characterized by autoimmune demyelinating events in the central nervous system. MS patients can present with a varying range of symptoms and disability due to the chronic inflammatory and relapsing events associated with the disease, such as impaired mobility, slowed cognitive processing, and high probability of disease progression.
 MS can be morphologically characterized by the damage to the myelin sheath that surrounds axons, oligodendrocytes that produce myelin, and axons that transmit information to different neurons. Due to the complicated mechanism of MS, the advanced MRI methods which can provide both sensitive and specific assessment of MS tissue injury hold the promise to provide critical mechanistic guidance of MS and serve as robust imaging biomarkers for MS. Several animal models have been established to understand the distinct aspects of the disease. Cuprizone, a copper chelator, creates demyelination events comparable to MS, allowing the mouse model to be a representation QSM’s ability to accurately distinguish between and predict acute and chronic demyelination events. Recently, we have demonstrated that the novel quantitative susceptibility mapping (QSM) can identify between the demyelination andremyelination process in the corpus callosum of mice treated with cuprizone. However, how early QSM can detect brain alterations has not been investigated.
 We acquired high-resolution in vivo whole-brain QSM, T-2 weighted, and magnetization transfer ratio (MTR) images at 0, 2, and 4 weeks after cuprizone administration. The corpus callosum exhibited significant changes in T2-weighted and MTR images at 4 weeks after cuprizone administration. In contrast, QSM decreased significantly in QSM at 2 weeks after cuprizone administration. Since dramatic demyelination only starts after oligodendrocytes depletion (3 weeks after cuprizone treatment), QSM may be able to detect the alteration of oligodendrocytes and serve as a sensitive biomarker even before demyelination occurs.

Triangulating brain alterations in anorexia nervosa: a multimodal investigation of magnetic resonance spectroscopy, morphometry and blood-based biomarkers

The acute state of anorexia nervosa (AN) is associated with widespread reductions in cortical gray matter (GM) thickness and white matter (WM) volume, suspected changes in myelin content and elevated levels of the neuronal damage marker neurofilament light (NF-L), but the underlying mechanisms remain largely unclear. To gain a deeper understanding of brain changes in AN, we applied a multimodal approach combining advanced neuroimaging methods with analysis of blood-derived biomarkers. In addition to standard measures of cortical GM thickness and WM volume, we analyzed tissue-specific profiles of brain metabolites using multivoxel proton magnetic resonance spectroscopy, T1 relaxation time as a proxy of myelin content leveraging advanced quantitative MRI methods and serum NF-L concentrations in a sample of 30 female, predominately adolescent patients with AN and 30 age-matched female healthy control participants. In patients with AN, we found a reduction in GM cortical thickness and GM total N-acetyl aspartate. The latter predicted higher NF-L levels, which were elevated in AN. Furthermore, GM total choline was elevated. In WM, there were no group differences in either imaging markers, choline levels or N-acetyl aspartate levels. The current study provides evidence for neuronal damage processes as well as for increased membrane lipid catabolism and turnover in GM in acute AN but no evidence for WM pathology. Our results illustrate the potential of multimodal research including tissue-specific proton magnetic resonance spectroscopy analyses to shed light on brain changes in psychiatric and neurological conditions, which may ultimately lead to better treatments.

Hybrid PET/MRI in Cerebral Glioma: Current Status and Perspectives.

Advanced MRI methods and PET using radiolabelled amino acids provide valuable information, in addition to conventional MR imaging, for brain tumour diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumour progression from treatment-related changes, and the early assessment of responses to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing, and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other, leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods, but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumours. PET is only required in equivocal situations, and the spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumours compared with a single modality. This review focuses on studies investigating the diagnostic value of combined amino acid PET and 'advanced' MRI in patients with cerebral gliomas. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterisation of newly diagnosed tumours. Few data are available concerning the delineation of tumour extent. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumour recurrence from treatment-related changes. Here, the PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of cerebral gliomas, for which hybrid PET/MRI offers optimal conditions.

Advanced neuroimaging in the fetal brain: An update on technical advances and clinical findings

AbstractMagnetic resonance imaging (MRI) is widely used to provide detailed information regarding fetal brain development in utero. Conventional T1‐and T2‐weighted sequences provide anatomical details of the normal brain and demonstrate brain lesions. In addition to providing highly detailed qualitative assessments of fetal brain development, advanced MRI methods such as three‐dimensional high‐resolution MRI, diffusion MRI, magnetic resonance spectroscopy, and functional MRI can provide quantitative morphologic assessments of tissue microstructure and functional activity. This review aims to describe normal fetal brain development and highlight current state‐of‐the‐art MRI sequences for fetal neuroimaging. We focus on current clinical applications which can provide a better understanding of in utero impairments in fetal brain development.

A longitudinal microstructural MRI dataset in healthy C57Bl/6 mice at 9.4 Tesla

Multimodal microstructural MRI has shown increased sensitivity and specificity to changes in various brain disease and injury models in the preclinical setting. Here, we present an in vivo longitudinal dataset, including a subset of ex vivo data, acquired as control data and to investigate microstructural changes in the healthy mouse brain. The dataset consists of structural T2-weighted imaging, magnetization transfer ratio and saturation imaging, and advanced quantitative diffusion MRI (dMRI) methods. The dMRI methods include oscillating gradient spin echo (OGSE) dMRI and microscopic anisotropy (μA) dMRI, which provide additional insight by increasing sensitivity to smaller spatial scales and disentangling fiber orientation dispersion from true microstructural changes, respectively. The technical skills required to analyze microstructural MRI data are complex and include MRI sequence development, acquisition, and computational neuroimaging expertise. Here, we share unprocessed and preprocessed data, and scalar maps of quantitative MRI metrics. We envision utility of this dataset in the microstructural MRI field to develop and test biophysical models, methods that model temporal brain dynamics, and registration and preprocessing pipelines.

Analysis of brain structural connectivity networks and white matter integrity in patients with mild cognitive impairment

AbstractBackgroundMild cognitive impairment (MCI) is considered a prodromal phase of Alzheimer’s disease (AD) and patients with MCI convert to AD at a rate of about 10–15% per year. Because of this high conversion rate to AD, studies of MCI may yield insight into early pathological changes in AD. Here, we used a novel approach to analyze structural connectivity and white matter (WM) integrity using fractional anisotropy (FA), intra‐cellular (IC), extra‐cellular (EC), and isotropic (ISO) maps between patients with MCI and healthy controls (HC).MethodThirty‐two HC (age mean ± S.D. = 69 ± 6 years; 22 females) and 20 MCI (71 ± 9 years; 7 females) were included in this study. All subjects completed the Mini‐Mental State Exam (MMSE) and the Montreal Cognitive Assessment (MoCA). Multi‐shell DTI were download from ADNI (http://adni.loni.usc.edu/). Pre‐processing was performed by Mrtrix3, FSL, and ANTs. Tractography was performed with 5 million seeds using the iFOD2 algorithm. Connectome was generated from the Desikan‐Killiany parcellation file and was subsequently filtered using the COMMIT2 algorithm. A three‐compartment Stick‐Zeppelin‐Ball model was used to create the IC, the EC, and the ISO compartments, respectively. Statistical analyses (ANCOVA) were performed by connectomestats (Mrtrix3), randomise (FLS), and by an in‐house Matlab script for Spearman’s correlations.ResultThe two groups did differ in MMSE and MoCA (Mann–Whitney U test: Z=2.031; p=0.021; Z=1.683; p=0.046, respectively). Differences between HC and MCI were found principally in the fornix for FA and in several WM areas for IC and ISO (Figure 1, Table 1). Connectometry analysis found differences between groups in two distinct tracts: Tract#1 between the left‐lateraloccipital and the left‐insula (t=4.25, p=0.023) and Tract#2 between the left‐middletemporal and the left‐parsopercularis (t=3.34, p=0.013) (Figure 2). Figure 3 and Table 2 show the results for the correlations between DTI metrics and the neurological scores.ConclusionIn this study, by using a multi‐shell diffusion MRI acquisition and robust processing of DTI data, we detected alterations in WM integrity and structural connectivity in MCI subjects. Our results demonstrate the potential of these advanced diffusion MRI methods as biomarkers to distinguish MCI and HC.

NIMG-05. DIFFERENCES IN VASCULARITY BETWEEN RECURRENT GLIOBLASTOMA AND BRAIN METASTASIS USING DYNAMIC CONTRAST ENHANCED MRI

Abstract In recent years, several automatic methods have been proposed to differentiate between brain tumor recurrence and treatment-related changes following radiotherapy, based on conventional and advanced MRI methods. Vascular parameters extracted from dynamic contrast-enhanced (DCE) were suggested as potential markers for disease progression. Yet, most studies that proposed machine-learning methods or relayed on threshold values of DCE for classification, did not analyze separately Glioblastoma (GBM) and brain metastasis, and often offer the same method/threshold values, neglecting the different vascularity of these two tumor types. Understanding and quantifying the differences between tumors type can improve early diagnosis of recurrence and may improve the reliability of identifying treatment-related changes. The aim of this study was to quantify vascular parameters of tumor recurrence and to assess differences between GBM and brain metastasis, specifically metastasis of breast cancer. METHOD: 41 MRI scans were included: 24 from patients with GBM: 20 with recurrence and 4 with treatment-related changes, and 17 scans from patients with brain metastasis of breast cancer: 10 with recurrence and 7 with treatment-related changes (diagnosis were based on radiological follow-up/histopathology, when available). MRIs were performed on a 3.0 Tesla MRI scanner (Siemens MAGNETOM Prisma) and included T1, T1+contrast, and DCE images. DCE analysis was performed using DUSTER and Ktrans, Vp and Kep pharmacokinetic parameters were compared between groups. RESULTS: Patients with GBM often demonstrated both tumor recurrence and areas with treatment-related changes. Significantly differences were detected between tumor recurrence and treatment-related changes, and higher Vp and Ktrans were detected in recurrent GBM as compared to recurrent breast cancer metastasis. Cutoff for differentiation between tumor recurrence and treatment-related changes will be presented specifically for each tumor type. To conclude, when defining quantitative threshold values for clinical decision-making, the inherent differences between primary and metastatic brain tumors should be taken into account.

A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis.

Multiple sclerosis (MS) lesions that do not resolve in the months after they form harbour ongoing demyelination and axon degeneration, and are identifiable in vivo by their paramagnetic rims on MRI scans1-3. Here, to define mechanisms underlying this disabling, progressive neurodegenerative state4-6 and foster development of new therapeutic agents, we used MRI-informed single-nucleus RNA sequencing to profile the edge of demyelinated white matter lesions at various stages of inflammation. We uncovered notable glial and immune cell diversity, especially at the chronically inflamed lesion edge. We define 'microglia inflamed in MS' (MIMS) and 'astrocytes inflamed in MS', glial phenotypes that demonstrate neurodegenerative programming. The MIMS transcriptional profile overlaps with that of microglia in other neurodegenerative diseases, suggesting that primary and secondary neurodegeneration share common mechanisms and could benefit from similar therapeutic approaches. We identify complement component 1q (C1q) as a critical mediator of MIMS activation, validated immunohistochemically in MS tissue, genetically by microglia-specific C1q ablation in mice with experimental autoimmune encephalomyelitis, and therapeutically by treating chronic experimental autoimmune encephalomyelitis with C1q blockade. C1q inhibition is a potential therapeutic avenue to address chronic white matter inflammation, which could be monitored by longitudinal assessment of its dynamic biomarker, paramagnetic rim lesions, using advanced MRI methods.

Neuroplasticity mediated by motor rehabilitation in Parkinson’s disease: a systematic review on structural and functional MRI markers

Parkinson's disease (PD) is the second most common neurological disease affecting the elderly population. Pharmacological and surgical interventions usually employed for PD treatment show transient effectiveness and are associated with the insurgence of side effects. Therefore, motor rehabilitation has been proposed as a promising supplement in the treatment of PD, reducing the global burden of the disease and improving patients quality of life. The present systematic review aimed to critically analyse the literature concerning MRI markers of brain functional and structural response to motor rehabilitation in PD. Fourteen out of 1313 studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Despite the limited number of retrieved studies coupled with their heterogeneity prevent ultimate conclusions from being drawn, motor rehabilitation seems to have beneficial effects on PD as measured both with clinical outcomes and MRI derived indices. Interestingly, consistent results seem to indicate that motor rehabilitation acts via a dual mechanism of strengthening cortico-subcortical pathways, restoring movements automaticity, or activating compensatory networks such as the fronto-parietal one. The employment of more advanced and quantitative MRI methods is warranted to establish and validate standardized metrics capable of reliably determining the changes induced by rehabilitative intervention.

Contributions of PET and MRI imaging in the evaluation of CNS drugs in human neurodegenerative diseases

This manuscript reviews the contributions of the neuroimaging methods including PET, conventional and advanced MRI methods to monitor the effect of new disease modifying drugs in neurodegenerative diseases. It now seems obvious that in many pathologies these two techniques are more and more complementary.

Along-tract statistics of neurite orientation dispersion and density imaging diffusion metrics to enhance MR tractography quantitative analysis in healthy controls and in patients with brain tumors.

Along‐tract statistics analysis enables the extraction of quantitative diffusion metrics along specific white matter fiber tracts. Besides quantitative metrics derived from classical diffusion tensor imaging (DTI), such as fractional anisotropy and diffusivities, new parameters reflecting the relative contribution of different diffusion compartments in the tissue can be estimated through advanced diffusion MRI methods as neurite orientation dispersion and density imaging (NODDI), leading to a more specific microstructural characterization. In this study, we extracted both DTI‐ and NODDI‐derived quantitative microstructural diffusion metrics along the most eloquent fiber tracts in 15 healthy subjects and in 22 patients with brain tumors. We obtained a robust intraprotocol reference database of normative along‐tract microstructural metrics, and their corresponding plots, from healthy fiber tracts. Each diffusion metric of individual patient's fiber tract was then plotted and statistically compared to the normative profile of the corresponding metric from the healthy fiber tracts. NODDI‐derived metrics appeared to account for the pathological microstructural changes of the peritumoral tissue more accurately than DTI‐derived ones. This approach may be useful for future studies that may compare healthy subjects to patients diagnosed with other pathological conditions.

Preliminary longitudinal analysis of knee articular cartilage and knee health in collegiate basketball players and swimmers

Purpose: Jumping and impact athletes put extra mechanical stress on their joints which can lead to chronic knee injuries. It has previously been seen that the risk for knee OA is higher in former male elite athletes compared with matched controls. Advanced MRI methods offer a way to non-invasively study early changes in knee articular cartilage and overall risk of degenerative disease progression. In this multi-center study, we use advanced quantitative MRI metrics of T1ρ and T2 to longitudinally study early cartilage changes in National Collegiate Athletic Association (NCAA) Division 1 (D1) basketball players compared with D1 swimmers.

Emerging advances of in vivo detection of chronic traumatic encephalopathy and traumatic brain injury.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder that is of epidemic proportions in contact sports athletes and is linked to subconcussive and concussive repetitive head impacts (RHI). Although postmortem analysis is currently the only confirmatory method to diagnose CTE, there has been progress in early detection techniques of fluid biomarkers as well as in advanced neuroimaging techniques. Specifically, promising new methods of diffusion MRI and radionucleotide PET scans could aid in the early detection of CTE.The authors examine early detection methods focusing on various neuroimaging techniques. Advances in structural and diffusion MRI have demonstrated the ability to measure volumetric and white matter abnormalities associated with CTE. Recent studies using radionucleotides such as flortaucipir and 18F-FDDNP have shown binding patterns that are consistent with the four stages of neurofibrillary tangle (NFT) distribution postmortem. Additional research undertakings focusing on fMRI, MR spectroscopy, susceptibility-weighted imaging, and singlephoton emission CT are also discussed as are advanced MRI methods such as diffusiontensor imaging and arterial spin labeled. Neuroimaging is fast becoming a key instrument in early detection and could prove essential for CTE quantification. This review explores a global approach to in vivo early detection.Limited data of in vivo CTE biomarkers with postmortem confirmation are available. While some data exist, they are limited by selection bias. It is unlikely that a single test will be sufficient to properly diagnosis and distinguish CTE from other neurodegenerative diseases such as Alzheimer disease or Frontotemporal Dementia. However, with a combination of fluid biomarkers, neuroimaging, and genetic testing, early detection may become possible.

TSPO-PET and diffusion-weighted MRI for imaging a mouse model of infiltrative human glioma.

Glioblastoma (GBM) is the most devastating brain tumor. Despite the use of multimodal treatments, most patients relapse, often due to the highly invasive nature of gliomas. However, the detection of glioma infiltration remains challenging. The aim of this study was to assess advanced PET and MRI techniques for visualizing biological activity and infiltration of the tumor. Using multimodality imaging, we investigated [18F]DPA-714, a radiotracer targeting the 18 kDa translocator protein (TSPO), [18F]FET PET, non-Gaussian diffusion MRI (apparent diffusion coefficient, kurtosis), and the S-index, a composite diffusion metric, to detect tumor infiltration in a human invasive glioma model. In vivo imaging findings were confirmed by autoradiography and immunofluorescence. Increased tumor-to-contralateral [18F]DPA-714 uptake ratios (1.49 ± 0.11) were found starting 7 weeks after glioma cell implantation. TSPO-PET allowed visualization of glioma infiltration into the contralateral hemisphere 2 weeks earlier compared with the clinically relevant biomarker for biological glioma activity [18F]FET. Diffusion-weighted imaging (DWI), in particular kurtosis, was more sensitive than standard T2-weighted MRI to detect differences between the glioma-bearing and the contralateral hemisphere at 5 weeks. Immunofluorescence data reflect in vivo findings. Interestingly, labeling for tumoral and stromal TSPO indicates a predominant expression of TSPO by tumor cells. These results suggest that advanced PET and MRI methods, such as [18F]DPA-714 and DWI, may be superior to standard imaging methods to visualize glioma growth and infiltration at an early stage.

Glioma response assessment: Classic pitfalls, novel confounders, and emerging imaging tools.

Neuroimaging plays a pivotal role in the care of patients with infiltrating gliomas, in whom imaging changes are often the first indications of tumor response or progression. Unfortunately, evaluation of glioma response is often not straightforward, even for experienced radiologists. Post-surgical or radiation-related changes may mimic the appearance of disease progression, while medications such as corticosteroids and antiangiogenic agents may mimic tumor response without truly arresting tumor growth or improving patient survival. Immunotherapy response can result in inflammatory changes which manifest as progressively increasing tumor enhancement and edema over months. Many of these pitfalls can be minimized or avoided altogether by the use of modern brain tumor response criteria, while others will require new imaging tools before they can be fully addressed. Advanced MRI methods and novel positron emission tomography (PET) agents are proving important for this purpose, and their role will undoubtedly continue to grow in the future.

Disruption of neurite morphology parallels MS progression.

ObjectivesTo apply advanced diffusion MRI methods to the study of normal-appearing brain tissue in MS and examine their correlation with measures of clinical disability.MethodsA multi-compartment model of diffusion MRI called neurite orientation dispersion and density imaging (NODDI) was used to study 20 patients with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS), and 20 healthy controls. Maps of NODDI were analyzed voxel-wise to assess the presence of abnormalities within the normal-appearing brain tissue and the association with disease severity. Standard diffusion tensor imaging (DTI) parameters were also computed for comparing the 2 techniques.ResultsPatients with MS showed reduced neurite density index (NDI) and increased orientation dispersion index (ODI) compared with controls in several brain areas (p < 0.05), with patients with SPMS having more widespread abnormalities. DTI indices were also sensitive to some changes. In addition, patients with SPMS showed reduced ODI in the thalamus and caudate nucleus. These abnormalities were associated with scores of disease severity (p < 0.05). The association with the MS functional composite score was higher in patients with SPMS compared with patients with RRMS.ConclusionsNODDI and DTI findings are largely overlapping. Nevertheless, NODDI helps interpret previous findings of increased anisotropy in the thalamus of patients with MS and are consistent with the degeneration of selective axon populations.

Assessing the predictability of IDH mutation and MGMT methylation status in glioma patients using relaxation-compensated multipool CEST MRI at 7.0 T.

Early identification of prognostic superior characteristics in glioma patients such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH mutation status, MGMT promoter methylation, and differentiation of low-grade versus high-grade glioma (LGG vs HGG) in newly diagnosed patients employing relaxation-compensated multipool chemical exchange saturation transfer (CEST) MRI at 7.0 Tesla. Thirty-one patients with newly diagnosed glioma were included in this prospective study. CEST MRI was performed at a 7T whole-body scanner. Nuclear Overhauser effect (NOE) and isolated amide proton transfer (APT; downfield NOE-suppressed APT = dns-APT) CEST signals (mean value and 90th signal percentile) were quantitatively investigated in the whole tumor area with regard to predictability of IDH mutation, MGMT promoter methylation status, and differentiation of LGG versus HGG. Statistics were performed using receiver operating characteristic (ROC) and area under the curve (AUC) analysis. Results were compared with advanced MRI methods (apparent diffusion coefficient and relative cerebral blood volume ROC/AUC analysis) obtained at 3T. dns-APT CEST yielded highest AUCs in IDH mutation status prediction (dns-APTmean = 91.84%, P < 0.01; dns-APT90 = 97.96%, P < 0.001). Furthermore, dns-APT metrics enabled significant differentiation of LGG versus HGG (AUC: dns-APTmean = 0.78, P < 0.05; dns-APT90 = 0.83, P < 0.05). There was no significant difference regarding MGMT promoter methylation status at any contrast (P > 0.05). Relaxation-compensated multipool CEST MRI, particularly dns-APT imaging, enabled prediction of IDH mutation status and differentiation of LGG versus HGG and should therefore be considered as a non-invasive MR biomarker in the diagnostic workup.