Coregistered histology sections with diffusion tensor imaging data at 200 µm resolution in meningioma tumors.

A significant problem in diffusion MRI (dMRI) is the lack of understanding regarding which microstructural features account for the variability in the diffusion tensor imaging (DTI) parameters observed in meningioma tumors. A common assumption is that mean diffusivity (MD) and fractional anisotropy (FA) from DTI are inversely proportional to cell density and proportional to tissue anisotropy, respectively. Although these associations have been established across a wide range of tumors, they have been challenged for interpreting within-tumor variations where several additional microstructural features have been suggested as contributing to MD and FA. To facilitate the investigation of the biological underpinnings of DTI parameters, we performed ex-vivo DTI at 200 µm isotropic resolution on sixteen excised meningioma tumor samples. The samples exhibit a variety of microstructural features because the dataset includes meningiomas of six different meningioma types and two different grades. Diffusion-weighted signal (DWI) maps, DWI maps averaged over all directions for given b-value, signal intensities without diffusion encoding (S0) as well as DTI parameters: MD, FA, in-plane FA (FAIP), axial diffusivity (AD) and radial diffusivity (RD), were coregistered to Hematoxylin & Eosin- (H&E) and Elastica van Gieson-stained (EVG) histological sections by a non-linear landmark-based approach. Here, we provide DWI signal and DTI maps coregistered to histology sections and describe the pipeline for processing the raw DTI data and the coregistration. The raw, processed, and coregistered data are hosted by Analytic Imaging Diagnostics Arena (AIDA) data hub registry, and software tools for processing are provided via GitHub. We hope that data can be used in research and education concerning the link between the meningioma microstructure and parameters obtained by DTI.

Associations Between CSF Markers of Inflammation, White Matter Lesions, and Cognitive Decline in Individuals Without Dementia.

BACKGROUND AND OBJECTIVES: Small vessel disease (SVD) and neuroinflammation both occur in Alzheimer disease (AD) and other neurodegenerative diseases. It is unclear whether these processes are related or independent mechanisms in AD, especially in the early stages of disease. We therefore investigated the association between white matter lesions (WML; the most common manifestation of SVD) and CSF biomarkers of neuroinflammation and their effects on cognition in a population without dementia. METHODS: Individuals without dementia from the Swedish BioFINDER study were included. The CSF was analyzed for proinflammatory markers (interleukin [IL]-6 and IL-8), cytokines (IL-7, IL-15, and IL-16), chemokines (interferon γ-induced protein 10, monocyte chemoattractant protein 1), markers of vascular injury (soluble intercellular adhesion molecule 1, soluble vascular adhesion molecule 1), and markers of angiogenesis (placental growth factor [PlGF], soluble fms-related tyrosine kinase 1 [sFlt-1], vascular endothelial growth factors [VEGF-A and VEFG-D]), and amyloid ß (Aß)42 Aß40, and p-tau217. WML volumes were determined at baseline and longitudinally over 6 years. Cognition was measured at baseline and follow-up over 8 years. Linear regression models were used to test associations. RESULTS: A total of 495 cognitively unimpaired (CU) elderly individuals and 247 patients with mild cognitive impairment (MCI) were included. There was significant worsening in cognition over time, measured by Mini-Mental State Examination, Clinical Dementia Rating, and modified preclinical Alzheimer composite score in CU individuals and patients with MCI, with more rapid worsening in MCI for all cognitive tests. At baseline, higher levels of PlGF (ß = 0.156, p < 0.001), lower levels of sFlt-1 (ß = -0.086, p = 0.003), and higher levels of IL-8 (ß = 0.07, p = 0.030) were associated with more WML in CU individuals. In those with MCI, higher levels of PlGF (ß = 0.172, p = 0.001), IL-16 (ß = 0.125, p = 0.001), IL-8 (ß = 0.096, p = 0.013), IL-6 (ß = 0.088, p = 0.023), VEGF-A (ß = 0.068, p = 0.028), and VEGF-D (ß = 0.082, p = 0.028) were associated with more WML. PlGF was the only biomarker that was associated with WML independent of Aß status and cognitive impairment. Longitudinal analyses of cognition showed independent effects of CSF inflammatory markers and WML on longitudinal cognition, especially in people without cognitive impairment at baseline. DISCUSSION: Most neuroinflammatory CSF biomarkers were associated with WML in individuals without dementia. Our findings especially highlight a role for PlGF, which was associated with WML independent of Aß status and cognitive impairment.

Meningioma microstructure assessed by diffusion MRI: An investigation of the source of mean diffusivity and fractional anisotropy by quantitative histology.

BACKGROUND: Mean diffusivity (MD) and fractional anisotropy (FA) from diffusion MRI (dMRI) have been associated with cell density and tissue anisotropy across tumors, but it is unknown whether these associations persist at the microscopic level. PURPOSE: To quantify the degree to which cell density and anisotropy, as determined from histology, account for the intra-tumor variability of MD and FA in meningioma tumors. Furthermore, to clarify whether other histological features account for additional intra-tumor variability of dMRI parameters. MATERIALS AND METHODS: We performed ex-vivo dMRI at 200 µm isotropic resolution and histological imaging of 16 excised meningioma tumor samples. Diffusion tensor imaging (DTI) was used to map MD and FA, as well as the in-plane FA (FAIP). Histology images were analyzed in terms of cell nuclei density (CD) and structure anisotropy (SA; obtained from structure tensor analysis) and were used separately in a regression analysis to predict MD and FAIP, respectively. A convolutional neural network (CNN) was also trained to predict the dMRI parameters from histology patches. The association between MRI and histology was analyzed in terms of out-of-sample (R2OS) on the intra-tumor level and within-sample R2 across tumors. Regions where the dMRI parameters were poorly predicted from histology were analyzed to identify features apart from CD and SA that could influence MD and FAIP, respectively. RESULTS: Cell density assessed by histology poorly explained intra-tumor variability of MD at the mesoscopic level (200 µm), as median R2OS = 0.04 (interquartile range 0.01-0.26). Structure anisotropy explained more of the variation in FAIP (median R2OS = 0.31, 0.20-0.42). Samples with low R2OS for FAIP exhibited low variations throughout the samples and thus low explainable variability, however, this was not the case for MD. Across tumors, CD and SA were clearly associated with MD (R2 = 0.60) and FAIP (R2 = 0.81), respectively. In 37% of the samples (6 out of 16), cell density did not explain intra-tumor variability of MD when compared to the degree explained by the CNN. Tumor vascularization, psammoma bodies, microcysts, and tissue cohesivity were associated with bias in MD prediction based solely on CD. Our results support that FAIP is high in the presence of elongated and aligned cell structures, but low otherwise. CONCLUSION: Cell density and structure anisotropy account for variability in MD and FAIP across tumors but cell density does not explain MD variations within the tumor, which means that low or high values of MD locally may not always reflect high or low tumor cell density. Features beyond cell density need to be considered when interpreting MD.

Diffusion tensor imaging in glioblastoma patients treated with volumetric modulated arc radiotherapy: a longitudinal study.

BACKGROUND: Chemo- and radiotherapy (RT) is standard treatment for patients with high-grade glioma, but may cause side-effects on the patient's cognitive function. AIM: Use of diffusion tensor imaging (DTI) to investigate the longitudinal changes in normal-appearing brain tissue in glioblastoma patients undergoing modern arc-based RT with volumetric modulated arc therapy (VMAT) or helical tomotherapy. MATERIALS AND METHODS: The study included 27 patients newly diagnosed with glioblastoma and planned for VMAT or tomotherapy. All subjects underwent magnetic resonance imaging at the start of RT and at week 3, 6, 15, and 26. Fourteen subjects were additionally imaged at week 52. The DTI data were co-registered to the dose distribution maps. Longitudinal changes in fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were assessed in the corpus callosum, the centrum semiovale, the hippocampus, and the amygdala. RESULTS: Significant longitudinal changes in FA, MD, and RD were mainly found in the corpus callosum. In the other examined brain structures, only sparse and transient changes were seen. No consistent correlations were found between biodose, age, or gender and changes in DTI parameters. CONCLUSION: Longitudinal changes in MD, FA, and RD were observed but only in a limited number of brain structures and the changes were smaller than expected from literature. The results suggest that modern, arc-based RT may have less negative effect on normal-appearing parts of the brain tissue up to 12 months after radiotherapy.

Whole-Body MRI Surveillance-Baseline Findings in the Swedish Multicentre Hereditary TP53-Related Cancer Syndrome Study (SWEP53).

A surveillance strategy of the heritable TP53-related cancer syndrome (hTP53rc), commonly referred to as the Li-Fraumeni syndrome (LFS), is studied in a prospective observational nationwide multi-centre study in Sweden (SWEP53). The aim of this sub-study is to evaluate whole-body MRI (WB-MRI) regarding the rate of malignant, indeterminate, and benign imaging findings and the associated further workup generated by the baseline examination. Individuals with hTP53rc were enrolled in a surveillance program including annual whole-body MRI (WB-MRI), brain-MRI, and in female carriers, dedicated breast MRI. A total of 68 adults ≥18 years old have been enrolled to date. Of these, 61 fulfilled the inclusion criteria for the baseline MRI scan. In total, 42 showed a normal scan, while 19 (31%) needed further workup, of whom three individuals (3/19 = 16%) were diagnosed with asymptomatic malignant tumours (thyroid cancer, disseminated upper GI cancer, and liver metastasis from a previous breast cancer). Forty-three participants were women, of whom 21 had performed risk-reducing mastectomy prior to inclusion. The remaining were monitored with breast MRI, and no breast tumours were detected on baseline MRI. WB-MRI has the potential to identify asymptomatic tumours in individuals with hTP53rc syndrome. The challenge is to adequately and efficiently investigate all indeterminate findings. Thus, a multidisciplinary team should be considered in surveillance programs for individuals with hTP53rc syndrome.

Glioma grading, molecular feature classification, and microstructural characterization using MR diffusional variance decomposition (DIVIDE) imaging.

OBJECTIVE: To evaluate the potential of diffusional variance decomposition (DIVIDE) for grading, molecular feature classification, and microstructural characterization of gliomas. MATERIALS AND METHODS: Participants with suspected gliomas underwent DIVIDE imaging, yielding parameter maps of fractional anisotropy (FA), mean diffusivity (MD), anisotropic mean kurtosis (MKA), isotropic mean kurtosis (MKI), total mean kurtosis (MKT), MKA/MKT, and microscopic fractional anisotropy (µFA). Tumor type and grade, isocitrate dehydrogenase (IDH) 1/2 mutant status, and the Ki-67 labeling index (Ki-67 LI) were determined after surgery. Statistical analysis included 33 high-grade gliomas (HGG) and 17 low-grade gliomas (LGG). Tumor diffusion metrics were compared between HGG and LGG, among grades, and between wild and mutated IDH types using appropriate tests according to normality assessment results. Receiver operating characteristic and Spearman correlation analysis were also used for statistical evaluations. RESULTS: FA, MD, MKA, MKI, MKT, µFA, and MKA/MKT differed between HGG and LGG (FA: p = 0.047; MD: p = 0.037, others p < 0.001), and among glioma grade II, III, and IV (FA: p = 0.048; MD: p = 0.038, others p < 0.001). All diffusion metrics differed between wild-type and mutated IDH tumors (MKI: p = 0.003; others: p < 0.001). The metrics that best discriminated between HGG and LGGs and between wild-type and mutated IDH tumors were MKT and FA respectively (area under the curve 0.866 and 0.881). All diffusion metrics except FA showed significant correlation with Ki-67 LI, and MKI had the highest correlation coefficient (rs = 0.618). CONCLUSION: DIVIDE is a promising technique for glioma characterization and diagnosis. KEY POINTS: • DIVIDE metrics MKI is related to cell density heterogeneity while MKA and µFA are related to cell eccentricity. • DIVIDE metrics can effectively differentiate LGG from HGG and IDH mutation from wild-type tumor, and showed significant correlation with the Ki-67 labeling index. • MKI was larger than MKA which indicates predominant cell density heterogeneity in gliomas. • MKA and MKI increased with grade or degree of malignancy, however with a relatively larger increase in the cell eccentricity metric MKA in relation to the cell density heterogeneity metric MKI.

Brain white matter lesions are associated with reduced hypothalamic volume and cranial radiotherapy in childhood-onset craniopharyngioma.

CONTEXT: White matter lesions (WML) are caused by obstruction of small cerebral vessels associated with stroke risk. Craniopharyngioma (CP) patients suffer from increased cerebrovascular mortality. OBJECTIVE: To investigate the effect of reduced HT volume and cranial radiotherapy (CRT) on WML in childhood-onset CP patients. DESIGN: A cross-sectional study of 41 patients (24 women) surgically treated childhood-onset CP in comparison to controls. SETTING: The South Medical Region of Sweden (2.5 million inhabitants). METHODS: With magnetic resonance imaging (MRI), we analysed qualitative measurement of WML based on the visual rating scale of Fazekas and quantitative automated segmentation of WML lesion. Also, measurement HT volume and of cardiovascular risk factors were analysed. RESULTS: Patients had a significant increase in WML volume (mL) (P = .001) compared to controls. Treatment with cranial radiotherapy (CRT) vs no CRT was associated with increased WML volume (P = .02) as well as higher Fazekas score (P = .001). WML volume increased with years after CRT (r = 0.39; P = .02), even after adjustment for fat mass and age. A reduced HT volume was associated with increased WML volume (r = -0.61, P < .001) and explained 26% of the variation (r2  = 0.26). Altogether, 47% of the WML volume was explained by age at investigation, HT volume and CRT. Patients with more WML also had higher cardiovascular risk. CONCLUSIONS: CRT may be associated directly with increased WML volume or indirectly with reduced HT volume associated with higher cardiovascular risk. Risk factors should be carefully monitored in these patients.

Longitudinal study of cognitive function in glioma patients treated with modern radiotherapy techniques and standard chemotherapy.

Introduction: Cognitive function is an important outcome measure in patients with brain tumor, providing information about the patient's clinical situation, treatment effects and possible progressive disease. The aim of this longitudinal study was to evaluate effects of the currently used radiation and chemotherapy treatment on cognitive function and to investigate associations between cognitive function at baseline and progression as well as overall survival.Methods: 32 patients newly diagnosed with malignant glioma were evaluated at baseline with CNS Vital Signs (CNS-VS), a computerized standardized neuropsychological test battery, prior to arc-based radiotherapy and concomitant chemotherapy with Temozolomide. CNS-VS measures the cognitive functions known to be affected in patients with brain tumor, covering nine cognitive domains. Follow-up cognitive evaluations were performed in 26 patients after 3.5 months and in 13 patients 1 year after treatment start.Results: Overall cognitive scores were lower in the studied patient cohort at baseline compared to standardized domain scores. At 3.5 months follow-up cognitive functioning was slightly decreased, but only in 1/9 cognitive domains - visual memory - where significant changes were found compared to baseline test results. Similarly, at 12 months follow-up no significant changes in cognitive test results were seen compared to baseline examination, except for a decrease in the visual memory domain. In relation to early progression, the most significant cognitive deficits were dysfunctional visual memory and low executive functioning at baseline. Low executive function at baseline correlated most significantly with shorter overall survival.Conclusion: The present study suggests that the currently used arc-based radiotherapy and chemotherapy might affect cognitive function less negatively than previously described during treatment and in the first year after treatment in malignant glioma patients. In general, a high cognitive test score at baseline was associated with longer time to progression and with longer survival.

Relationship between cortical iron and tau aggregation in Alzheimer's disease.

A growing body of evidence suggests that the dysregulation of neuronal iron may play a critical role in Alzheimer's disease. Recent MRI studies have established a relationship between iron accumulation and amyloid-ß aggregation. The present study provides further insight demonstrating a relationship between iron and tau accumulation using magnetic resonance-based quantitative susceptibility mapping and tau-PET in n = 236 subjects with amyloid-ß pathology (from the Swedish BioFINDER-2 study). Both voxel-wise and regional analyses showed a consistent association between differences in bulk magnetic susceptibility, which can be primarily ascribed to an increase in iron content, and tau-PET signal in regions known to be affected in Alzheimer's disease. Subsequent analyses revealed that quantitative susceptibility specifically mediates the relationship between tau-PET and cortical atrophy measures, thus suggesting a modulatory effect of iron burden on the disease process. We also found evidence suggesting the relationship between quantitative susceptibility and tau-PET is stronger in younger participants (age ≤ 65). Together, these results provide in vivo evidence of an association between iron deposition and both tau aggregation and neurodegeneration, which help advance our understanding of the role of iron dysregulation in the Alzheimer's disease aetiology.

[Episodes with goose bumps caused by anti-LGI-1 encephalitis]. / Anfall av gåshud visade sig vara anti-LGI-1-encefalit.

Anti-LGI-1 encephalitis is a type of autoimmune encephalopathy, where antibodies react against the cell surface protein leucine-rich glioma inactivated protein 1 (LGI-1). It presents with a subacute confusion, changes in behaviour, short-term memory deficits and seizures. A piloerectile semiology is common, which has been described as reflecting insular ictal activity. Patients may have temporal lobe abnormalities on brain MRI and EEG. More than half of the patients with limbic encephalitis associated with anti-LGI1 antibodies have hyponatremia. The diagnosis of anti-LGI-1 encephalitis can be made by the detection of antibodies against LGI-1 in serum and/or cerebrospinal fluid. Prompt diagnosis and treatment are important to avoid long-term disability. This case report describes a man with episodes of goose bumps and mild confusion caused by anti-LGI-1 encephalitis.

Tensor-valued diffusion MRI in under 3 minutes: an initial survey of microscopic anisotropy and tissue heterogeneity in intracranial tumors.

PURPOSE: To evaluate the feasibility of a 3-minutes protocol for assessment of the microscopic anisotropy and tissue heterogeneity based on tensor-valued diffusion MRI in a wide range of intracranial tumors. METHODS: B-tensor encoding was performed in 42 patients with intracranial tumors (gliomas, meningiomas, adenomas, and metastases). Microscopic anisotropy and tissue heterogeneity were evaluated by estimating the anisotropic kurtosis (MKA ) and isotropic kurtosis (MKI ), respectively. An extensive imaging protocol was compared with a 3-minutes protocol. RESULTS: The fast imaging protocol yielded parameters with characteristics in terms of bias and precision similar to the full protocol. Glioblastomas had lower microscopic anisotropy than meningiomas (MKA = 0.29 ± 0.06 vs. 0.45 ± 0.08, P = 0.003). Metastases had higher tissue heterogeneity (MKI = 0.57 ± 0.07) than both the glioblastomas (0.44 ± 0.06, P < 0.001) and meningiomas (0.46 ± 0.06, P = 0.03). CONCLUSION: Evaluation of the microscopic anisotropy and tissue heterogeneity in intracranial tumor patients is feasible in clinically relevant times frames.

Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia.

OBJECTIVE: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies. METHODS: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991-1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), ß-amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009-2015). RESULTS: During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03-1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10-1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77-1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3-graded score (adjusted HR = 1.90 [95% CI = 1.07-3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05-2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87-1.90] for Aß42 and 1.35 [95% CI = 0.86-2.13] for Aß42 /p-tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies. INTERPRETATION: Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. ANN NEUROL 2020;87:52-62.

Diagnostic value of alternative techniques to gadolinium-based contrast agents in MR neuroimaging-a comprehensive overview.

Gadolinium-based contrast agents (GBCAs) increase lesion detection and improve disease characterization for many cerebral pathologies investigated with MRI. These agents, introduced in the late 1980s, are in wide use today. However, some non-ionic linear GBCAs have been associated with the development of nephrogenic systemic fibrosis in patients with kidney failure. Gadolinium deposition has also been found in deep brain structures, although it is of unclear clinical relevance. Hence, new guidelines from the International Society for Magnetic Resonance in Medicine advocate cautious use of GBCA in clinical and research practice. Some linear GBCAs were restricted from use by the European Medicines Agency (EMA) in 2017.This review focuses on non-contrast-enhanced MRI techniques that can serve as alternatives for the use of GBCAs. Clinical studies on the diagnostic performance of non-contrast-enhanced as well as contrast-enhanced MRI methods, both well established and newly proposed, were included. Advantages and disadvantages together with the diagnostic performance of each method are detailed. Non-contrast-enhanced MRIs discussed in this review are arterial spin labeling (ASL), time of flight (TOF), phase contrast (PC), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), susceptibility weighted imaging (SWI), and amide proton transfer (APT) imaging.Ten common diseases were identified for which studies reported comparisons of non-contrast-enhanced and contrast-enhanced MRI. These specific diseases include primary brain tumors, metastases, abscess, multiple sclerosis, and vascular conditions such as aneurysm, arteriovenous malformation, arteriovenous fistula, intracranial carotid artery occlusive disease, hemorrhagic, and ischemic stroke.In general, non-contrast-enhanced techniques showed comparable diagnostic performance to contrast-enhanced MRI for specific diagnostic questions. However, some diagnoses still require contrast-enhanced imaging for a complete examination.

Microstructural white matter alterations associated to neurocognitive deficits in childhood leukemia survivors treated with cranial radiotherapy - a diffusional kurtosis study.

Background: Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) are MRI techniques that quantify microstructural changes in brain white matter (WM) and DKI is regarded as the more sensitive of them. Our aim was to more thoroughly understand the nature of cognitive deficits after cranial radiotherapy (CRT) in adulthood after childhood ALL. Material and methods: Thirty-eight (21 women) ALL survivors, median age 38 (27-46) years, were investigated at median 34 years after diagnosis. All had been treated with a CRT dose of 24 Gy and with 11 years of complete hormone supplementation. DTI and DKI parameters were determined and neurocognitive tests were performed in ALL survivors and 29 matched controls. Results: ALL survivors scored lower than controls in neurocognitive tests of vocabulary, memory, learning capacity, spatial ability, executive functions, and attention (p < .001). The survivors had altered DTI parameters in the fornix, uncinate fasciculus, and ventral cingulum (all p < .05) and altered DKI parameters in the fornix, uncinate fasciculus, and dorsal and ventral cingulum (p < .05). Altered DTI parameters in the fornix were associated with impaired episodic verbal memory (r = -0.40, p < .04). The left and right uncinate fasciculus (r = 0.6, p < .001), (r = -0.5, p < .02) as well as the right ventral cingulum (r = 0.5, p < .007) were associated with impaired episodic visual memory. Altered DKI parameters in the fornix, right uncinate fasciculus (r = 0.3, r = 0.05, p = .02), and ventral cingulum (r = 0.3, p = .02) were associated with impaired results of episodic visual memory. Conclusion: ALL survivors with cognitive deficits demonstrated microstructural damage in several WM tracts that were more extensive with DKI as compared to DTI; this might be a marker of radiation and chemotherapy neurotoxicity underlying cognitive dysfunction.

Arterial spin labeling MR imaging for differentiation between high- and low-grade glioma-a meta-analysis.

Background: Arterial spin labeling is an MR imaging technique that measures cerebral blood flow (CBF) non-invasively. The aim of the study is to assess the diagnostic performance of arterial spin labeling (ASL) MR imaging for differentiation between high-grade glioma and low-grade glioma. Methods: Cochrane Library, Embase, Medline, and Web of Science Core Collection were searched. Study selection ended November 2017. This study was prospectively registered in PROSPERO (CRD42017080885). Two authors screened all titles and abstracts for possible inclusion. Data were extracted independently by 2 authors. Bivariate random effects meta-analysis was used to describe summary receiver operating characteristics. Trial sequential analysis (TSA) was performed. Results: In total, 15 studies with 505 patients were included. The diagnostic performance of ASL CBF for glioma grading was 0.90 with summary sensitivity 0.89 (0.79-0.90) and specificity 0.80 (0.72-0.89). The diagnostic performance was similar between pulsed ASL (AUC 0.90) with a sensitivity 0.85 (0.71-0.91) and specificity 0.83 (0.69-0.92) and pseudocontinuous ASL (AUC 0.88) with a sensitivity 0.86 (0.79-0.91) and specificity 0.80 (0.65-0.87). In astrocytomas, the diagnostic performance was 0.89 with sensitivity 0.86 (0.79 to 0.91) and specificity 0.79 (0.63 to 0.89). Sensitivity analysis confirmed the robustness of the findings. TSA revealed that the meta-analysis was adequately powered. Conclusion: Arterial spin labeling MR imaging had an excellent diagnostic accuracy for differentiation between high-grade and low-grade glioma. Given its low cost, non-invasiveness, and efficacy, ASL MR imaging should be considered for implementation in the routine workup of patients with glioma.

Imaging brain tumour microstructure.

Imaging is an indispensable tool for brain tumour diagnosis, surgical planning, and follow-up. Definite diagnosis, however, often demands histopathological analysis of microscopic features of tissue samples, which have to be obtained by invasive means. A non-invasive alternative may be to probe corresponding microscopic tissue characteristics by MRI, or so called 'microstructure imaging'. The promise of microstructure imaging is one of 'virtual biopsy' with the goal to offset the need for invasive procedures in favour of imaging that can guide pre-surgical planning and can be repeated longitudinally to monitor and predict treatment response. The exploration of such methods is motivated by the striking link between parameters from MRI and tumour histology, for example the correlation between the apparent diffusion coefficient and cellularity. Recent microstructure imaging techniques probe even more subtle and specific features, providing parameters associated to cell shape, size, permeability, and volume distributions. However, the range of scenarios in which these techniques provide reliable imaging biomarkers that can be used to test medical hypotheses or support clinical decisions is yet unknown. Accurate microstructure imaging may moreover require acquisitions that go beyond conventional data acquisition strategies. This review covers a wide range of candidate microstructure imaging methods based on diffusion MRI and relaxometry, and explores advantages, challenges, and potential pitfalls in brain tumour microstructure imaging.

Glioma Grade Discrimination with MR Diffusion Kurtosis Imaging: A Meta-Analysis of Diagnostic Accuracy.

Purpose To assess the diagnostic test accuracy and sources of heterogeneity for the discriminative potential of diffusion kurtosis imaging (DKI) to differentiate low-grade glioma (LGG) (World Health Organization [WHO] grade II) from high-grade glioma (HGG) (WHO grade III or IV). Materials and Methods The Cochrane Library, Embase, Medline, and the Web of Science Core Collection were systematically searched by two librarians. Retrieved hits were screened for inclusion and were evaluated with the revised tool for quality assessment for diagnostic accuracy studies (commonly known as QUADAS-2) by two researchers. Statistical analysis comprised a random-effects model with associated heterogeneity analysis for mean differences in mean kurtosis (MK) in patients with LGG or HGG. A bivariate restricted maximum likelihood estimation method was used to describe the summary receiver operating characteristics curve and bivariate meta-regression. Results Ten studies involving 430 patients were included. The mean difference in MK between LGG and HGG was 0.17 (95% confidence interval [CI]: 0.11, 0.22) with a z score equal to 5.86 (P < .001). The statistical heterogeneity was explained by glioma subtype, echo time, and the proportion of recurrent glioma versus primary glioma. The pooled area under the curve was 0.94 for discrimination of HGG from LGG, with 0.85 (95% CI: 0.74, 0.92) sensitivity and 0.92 (95% CI: 0.81, 0.96) specificity. Heterogeneity was driven by neuropathologic subtype and DKI technique. Conclusion MK shows high diagnostic accuracy in the discrimination of LGG from HGG. © RSNA, 2017 Online supplemental material is available for this article.

Diffusion Kurtosis Imaging of Gliomas Grades II and III - A Study of Perilesional Tumor Infiltration, Tumor Grades and Subtypes at Clinical Presentation.

BACKGROUND: Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas). PATIENTS AND METHODS: Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t-test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves. RESULTS: There were significant differences in all mean DKI variables between perilesional and contralesional NAWM (p=<0.000), except for axial kurtosis (p=0.099). Forty-four histogram variables differed significantly between glioma grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815. CONCLUSIONS: Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes.

A Functional MRI-Based Model for Individual Memory Assessment in Patients Eligible for Anterior Temporal Lobe Resection.

TITLE: A functional (f) MRI-based model for individual memory assessment in patients eligible for temporal lobe resection. AIM: To investigate if pre-operative fMRI memory paradigms, add predictive information with regard to post-surgical memory deficits. METHODS: Fourteen pharmacoresistant Temporal Lobe Epilepsy (TLE) patients accepted for Anterior Temporal Lobe Resection (ATLR) were included. A clinical risk assessment score (RAS 0-3) was constructed from structural MRI, neuropsychological testing and hemisphere dominance. fMRI lateralization indices (LIs) over frontal language and medial temporal regions were calculated. Predictive value from clinical risk scoring and added value from fMRI LIs were correlated to post-surgical memory change scores (significant decline -1 SD). Verbal memory outcome was classified either as expected (RAS 2-3 and post-operative decline; RAS 0-1 and intact post-operative verbal memory) or as unexpected (RAS 2-3 and intact post-operative verbal memory post-surgery; RAS 0-1 and post-operative decline). RESULTS: RAS for verbal memory decline exhibited a specificity of 67% and a sensitivity of 75%. Significant correlations were found between frontal language LIs and post-operative verbal memory (r = -0.802; p = 0.017) for left (L) TLE and between medial temporal lobe LIs and visuospatial memory (r = 0.829; p = 0.021), as well as verbal memory (r = 0.714; p = 0.055) for right (R) TLE. Ten patients had expected outcome and four patients had an unexpected outcome. In two MRI-negative RTLE patients that suffered significant verbal memory decline post-operatively, fMRI identified bilateral language and right lateralized medial temporal verbal encoding. In two LTLE patients with MRI pathology and verbal memory dysfunction, neither RAS nor fMRI identified the risk for aggravated verbal memory decline following ATLR. CONCLUSION: fMRI visualization of temporal-frontal network activation may add value to the pre-surgical work-up in epilepsy patients eligible for ATLR. Frontal language patterns are important for prediction in both L and RTLE. Strong left lateralized language in LTLE, as well as bilateral language combined with right lateralized encoding in RTLE, seems to indicate an increased risk for post-operative verbal memory decline.

Microstructure alterations in the hypothalamus in cranially radiated childhood leukaemia survivors but not in craniopharyngioma patients unaffected by hypothalamic damage.

OBJECTIVE: Metabolic complications are frequent in childhood leukaemia (ALL) survivors treated with cranial radiotherapy (CRT). These complications are potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO) craniopharyngioma (CP) survivors without HT involvement are spared overt obesity. Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We used DTI to determine the integrity of the microstructure of the HT in ALL survivors. DESIGN: Case-control study. PATIENTS: Three groups were included: (i) 27 CRT treated ALL survivors on hormone supplementation, (ii) 17 CO-CP survivors on hormone supplementation but without HT involvement and (iii) 27 matched controls. MEASUREMENTS: DTI parameters of the HT were measured and body composition. RESULTS: Microstructural alterations in the HT were more severe in ALL survivors with a BMI ≥25 than with BMI <25. Compared to controls, ALL survivors had reduced FA (P=.04), increased MD (P<.001), AD (P<.001) and RD (P<.001) in the right and left HT. In the right HT, ALL survivors with a BMI ≥25 showed elevated MD (P=.03) and AD (P=.02) compared to ALL survivors with BMI <25. In contrast, DTI parameters did not differ between CP survivors and controls. CONCLUSIONS: Long-term follow-up after CRT for ALL DTI measures were affected in the HT despite complete hormone replacement. The present data suggest that ALL survivors have demyelination and axonal loss in the HT.