Coupling between cerebrovascular oscillations and CSF flow fluctuations during wakefulness: An fMRI study

It is commonly believed that cerebrospinal fluid (CSF) movement is facilitated by blood vessel wall movements (i.e., hemodynamic oscillations) in the brain. A coherent pattern of low frequency hemodynamic oscillations and CSF movement was recently found during non-rapid eye movement (NREM) sleep via functional MRI. This finding raises other fundamental questions: 1) the explanation of coupling between hemodynamic oscillations and CSF movement from fMRI signals; 2) the existence of the coupling during wakefulness; 3) the direction of CSF movement. In this resting state fMRI study, we proposed a mechanical model to explain the coupling between hemodynamics and CSF movement through the lens of fMRI. Time delays between CSF movement and global hemodynamics were calculated. The observed delays between hemodynamics and CSF movement match those predicted by the model. Moreover, by conducting separate fMRI scans of the brain and neck, we confirmed the low frequency CSF movement at the fourth ventricle is bidirectional. Our finding also demonstrates that CSF movement is facilitated by changes in cerebral blood volume mainly in the low frequency range, even when the individual is awake.

Contribution of advanced neuro-imaging (MR diffusion, perfusion and proton spectroscopy) in differentiation between low grade gliomas GII and MR morphologically similar non neoplastic lesions

Background Non-neoplastic brain lesions can be misdiagnosed as low-grade gliomas. Conventional magnetic resonance (MR) imaging may be non-specific. Additional imaging modalities such as spectroscopy (MRS), perfusion and diffusion imaging aid in diagnosis of such lesions. However, contradictory and overlapping results are still present. Hence, our purpose was to evaluate the role of advanced neuro-imaging in differentiation between low-grade gliomas (WHO grade II) and MR morphologically similar non-neoplastic lesions and to prove which modality has the most accurate results in differentiation. Results All patients were classified into two main groups: patients with low-grade glioma (n = 12; mean age, 38.8 ± 16; 8 males) and patients with non-neoplastic lesions (n = 27; mean age, 36.6 ± 15; 19 males) based on the histopathological and clinical–radiological diagnosis. Using ROC curve analysis, a threshold value of 0.93 for rCBV (AUC = 0.875, PPV = 92%, NPV = 71.4%) and a threshold value of 2.5 for Cho/NAA (AUC = 0.829, PPV = 92%, NPV = 71.4%) had 85.2% sensitivity and 83.3% specificity for predicting neoplastic lesions. The area under the curve (AUC) of ROC analysis was good for relative cerebral blood volume (rCBV) and Cho/NAA ratios (> 0.80) and fair for Cho/Cr and NAA/Cr ratios (0.70–0.80). When the rCBV measurements were combined with MRS ratios, significant improvement was observed in the area under the curve (AUC) (0.969) with improved diagnostic accuracy (89.7%) and sensitivity (88.9%). Conclusions Evaluation of rCBV and metabolite ratios at MRS, particularly Cho/NAA ratio, may be helpful in differentiating low-grade gliomas from non-neoplastic lesions. The combination of dynamic susceptibility contrast (DSC) perfusion and MRS can significantly improve the diagnostic accuracy and can help avoiding the need for an invasive biopsy.

Local detection of microvessels in IDH-wildtype glioblastoma using relative cerebral blood volume: an imaging marker useful for astrocytoma grade 4 classification

Background The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification. Methods Data from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts’ supervision, achieving an accuracy of 88.8% of overlay. Spearman’s correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples. Results Significant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks (p < 0.001), as well as significant differences in rCBV were found between blocks with microvascular proliferation and blocks without it (p < 0.0001). In addition, significant differences in rCBV were found between IDH-wildtype glioblastoma and IDH-mutant astrocytoma samples, being 2–2.5 times higher rCBV values in IDH-wildtype glioblastoma samples. Conclusions The proposed rCBV marker, calculated from diagnostic MRIs, can detect in IDH-wildtype glioblastoma those regions with microvessels from those without it, and it is significantly correlated with local microvessels area. In addition, the proposed rCBV marker can differentiate the IDH mutation status, providing a complementary non-invasive method for high-grade glioma classification.

Comparison of MR Perfusion and FDG-PET Brain Studies in Patients With Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

Background: The aim of this study was to compare Dynamic Susceptibility Contrast Enhanced MRI (DSC-MRI) and PET with flurodeoxyglucose (FDG-PET) in the diagnosis of Alzheimer’s Disease (AD) and amnestic Mild Cognitive Impairment (aMCI).Methods: Age and sex matched 27 patients with AD, 39 with aMCI and 16 controls underwent brain DSC-MRI followed by FDG-PET. Values of relative Cerebral Blood Volume (rCBV) and rCBV z-scores from frontal, temporal, parietal and PCG cortices were correlated with the rate of glucose metabolism from PET. Sensitivity, specificity and accuracy of DSC-MRI and FDG-PET in the diagnosis of AD and aMCI were assessed and compared.Results: In AD hypoperfusion was found within all examined locations, while in aMCI in both parietal and temporal cortices and left PCG. FDG-PET showed the greatest hypometabolism in parietal, temporal and left PCG regions in both AD and aMCI. FDG-PET was more accurate in distinguishing aMCI from controls than DSC-MRI. In AD and combined group (AD + aMCI ) there were numerous correlations between DSC-MRI and FDG-PET results. Conclusions: In AD the patterns of hypoperfusion and glucose hypometabolism are similar thus DSC-MRI may be a competitive method to FDG-PET. FDG-PET is a more accurate method in the diagnosis of aMCI.

Prevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow)

BackgroundThe relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiological features of this phenomenon, and its associations with outcomes in three international randomized controlled thrombectomy trials with pre-specified follow-up perfusion imaging.MethodsIn a pooled analysis of the EXTEND-IA (ClinicalTrials.gov number NCT01492725), EXTEND-IA TNK (NCT02388061) and EXTEND-IA TNK Part-two (NCT03340493) trials, patients undergoing thrombectomy with final angiographic extended Thrombolysis In Cerebral Ischemia 2c-3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative Cerebral Blood Volume or Flow maps within the infarct and verified quantitatively by >15% asymmetry compared to a mirror homologue in the absence of carotid stenosis or re-occlusion.ResultsRegions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (Interquartile range 47.8-70.7%) of the infarct volume, and involved both subcortical (n=26/33,78.8%) and cortical (n=10/33,30.3%) regions. Patients with no-reflow had a median 25.2% ([Interquartile range 16.4-32.2%],p<0.00001) relative Cerebral Blood Volume interside reduction and 19.1% (Interquartile range 3.9-28.3%,p=0.00011) relative Cerebral Blood Flow reduction but similar mean-transit-time (median -3.3%, Interquartile range -11.9-24.4%,p=0.24) within the infarcted region. Baseline characteristics were similar between patients with and without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (aOR=1.79,95%CI2.32-15.57,p=0.0002), greater infarct growth (ß=11.00,95%CI5.22-16.78,p=0.00027), reduced National Institutes of Health Stroke Score improvement at 24-hours (ß=-4.06,95%CI-6.78--1.34,p=0.004) and being dependent or dead at 90-day as assessed on the modified Rankin Scale (aOR=3.72,95%CI1.35-10.20,p=0.011) in multivariable analysis.ConclusionCerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with post-treatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted.Classification of evidenceThis study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24-hours is associated with post-treatment complications and poor 3-month functional outcome.

A Comparison of Single- and Multiparametric MRI Models for Differentiation of Recurrent Glioblastoma from Treatment-Related Change

To evaluate single- and multiparametric MRI models to differentiate recurrent glioblastoma (GBM) and treatment-related changes (TRC) in clinical routine imaging. Selective and unselective apparent diffusion coefficient (ADC) and minimum, mean, and maximum cerebral blood volume (CBV) measurements in the lesion were performed. Minimum, mean, and maximum ratiosCBV (CBVlesion to CBVhealthy white matter) were computed. All data were tested for lesion discrimination. A multiparametric model was compiled via multiple logistic regression using data demonstrating significant difference between GBM and TRC and tested for its diagnostic strength in an independent patient cohort. A total of 34 patients (17 patients with recurrent GBM and 17 patients with TRC) were included. ADC measurements showed no significant difference between both entities. All CBV and ratiosCBV measurements were significantly higher in patients with recurrent GBM than TRC. A minimum CBV of 8.5, mean CBV of 116.5, maximum CBV of 327 and ratioCBV minimum of 0.17, ratioCBV mean of 2.26 and ratioCBV maximum of 3.82 were computed as optimal cut-off values. By integrating these parameters in a multiparametric model and testing it in an independent patient cohort, 9 of 10 patients, i.e., 90%, were classified correctly. The multiparametric model further improves radiological discrimination of GBM from TRC in comparison to single-parameter approaches and enables reliable identification of recurrent tumors.

Intensity distribution segmentation in Ultrafast Doppler and correlative Scanning Laser Confocal Microscopy for assessing vascular changes associated with ageing in murine hippocampi

The hippocampus plays an important role in learning and memory, requiring high-neuronal oxygenation. Understanding the relationship between blood flow and vascular structure – and how it changes with ageing – is physiologically and anatomically relevant. Ultrafast Doppler (µDoppler) and Scanning Laser Confocal Microscopy (SLCM) are powerful imaging modalities that can measure in-vivo Cerebral Blood Volume (CBV) and ex-vivo vascular structure, respectively. Here, we apply both imaging modalities to a cross-sectional and longitudinal study of hippocampi vasculature in wild-type mice brains. We introduce a segmentation of CBV distribution obtained from µDoppler and show that this mice-independent and mesoscopic measurement is correlated with the number of vessels and Vessel Volume Fraction (VVF) distributions obtained from SLCM – e.g., high CBV relates to fewer number of vessels but with large VVF. Moreover, we find significant changes in CBV distribution and vasculature due to ageing (5 vs. 21 month-old mice), highlighting the sensitivity of our approach. Overall, we are able to associate CBV with vascular structure – and track its longitudinal changes – at the artery-vein, venules, arteriole, and capillary levels. We believe that this correlative approach can be a powerful tool for studying other acute (e.g., brain injuries), progressive (e.g., neurodegeneration) or induced pathological changes.

Perfusion CT detects alterations in local cerebral flow of glioma related to IDH, MGMT and TERT status

Background The aim of this study was to investigate the relationship between tumor biology and values of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), time to peak (TTP), permeability surface (PS) of tumor in patients with glioma. Methods Forty-six patients with glioma were involved in the study. Histopathologic and molecular pathology diagnoses were obtained by tumor resection, and all patients accepted perfusion computed tomography (PCT) before operation. Regions of interests were placed manually at tumor and contralateral normal-appearing thalamus. The parameters of tumor were divided by those of contralateral normal-appearing thalamus to normalize at tumor (relative [r] CBV, rCBF, rMTT, rTTP, rPS). The relationships of the parameters, world health organization (WHO) grade, molecular pathological findings were analysed. Results The rCBV, rMTT and rPS of patients are positively related to the pathological classification (P < 0.05). The values of rCBV and rPS in IDH mutated patients were lower than those IDH wild-type. The values of rCBF in patients with MGMT methylation were lower than those MGMT unmethylation (P < 0.05). The MVD of TERT wild-type group was lower than TERT mutated group (P < 0.05). The values of rCBV were significant difference in the four molecular groups divided by the combined IDH/TERT classification (P < 0.05). The progression free survival (PFS) and overall survival (OS) were significant difference in the four molecular groups divided by the combined IDH/TERT classification (P < 0.05). Conclusions Our study introduces and supports the changes of glioma flow perfusion may be closely related to its biological characteristics.