Attenuation of the BOLD fMRI Signal and Changes in Functional Connectivity Affecting the Whole Brain in Presence of Brain Metastasis.

To date, there are almost no investigations addressing functional connectivity (FC) in patients with brain metastases (BM). In this retrospective study, we investigate the influence of BM on hemodynamic brain signals derived from functional magnetic resonance imaging (fMRI) and FC. Motor-fMRI data of 29 patients with BM and 29 matched healthy controls were analyzed to assess percent signal changes (PSC) in the ROIs motor cortex, premotor cortex, and supplementary motor cortex and FC in the sensorimotor, default mode, and salience networks using Statistical Parametric Mapping (SPM12) and marsbar and CONN toolboxes. In the PSC analysis, an attenuation of the BOLD signal in the metastases-affected hemisphere compared to the contralateral hemisphere was significant only in the supplementary motor cortex during hand movement. In the FC analysis, we found alterations in patients' FC compared to controls in all examined networks, also in the hemisphere contralateral to the metastasis. This indicates a qualitative attenuation of the BOLD signal in the affected hemisphere and also that FC is altered by the presence of BM, similarly to what is known for primary brain tumors. This transformation is not only visible in the infiltrated hemisphere, but also in the contralateral one, suggesting an influence of BM beyond local damage.

Analysis of Functional Neuroplastic Changes in the Cortical Language System in Relation to Different Growth Patterns of Glioblastoma.

The interpretation of fMRI data in glioblastoma (GB) is challenging as these tumors exhibit specific hemodynamic processes which, together with malignancy, tumor volume and proximity to eloquent cortex areas, may lead to misinterpretations of fMRI signals. The aim of this study was to investigate if different radiologically defined GB tumor growth patterns may also influence the fMRI signal, activation pattern and functional connectivity differently. Sixty-four patients with left-hemispheric glioblastoma were included and stratified according to their radiologically defined tumor growth pattern into groups with a uniform (U-TGP) or diffuse tumor growth pattern (D-TGP). Task-based fMRI data were analyzed using SPM12 with the marsbar, LI and CONN toolboxes. The percent signal change and the laterality index were analyzed, as well as functional connectivity between 23 selected ROIs. Comparisons of both patient groups showed only minor non-significant differences, indicating that the tumor growth pattern is not a relevant influencing factor for fMRI signal. In addition to these results, signal reductions were found in areas that were not affected by the tumor underlining that a GB is not a localized but rather a systemic disease affecting the entire brain.

Multiparametric Magnetic Resonance Imaging of the Kidneys: Effects of Regional, Side, and Hydration Variations on Functional Quantifications.

BACKGROUND: To standardize renal functional magnetic resonance imaging (MRI), it is important to understand the influence of side-to-side variation, regional variation within the organ, and hydration states in MRI and to search for variables that are not affected by those variations. PURPOSE: To assess MRI-based biomarkers for characterizing the kidney in healthy volunteers while considering variations in anatomic factors and hydration states. STUDY TYPE: Prospective. SUBJECTS: Twenty-five healthy volunteers (15 females and 10 males, median age 25 years). FIELD STRENGTH/SEQUENCE: 3.0 T intravoxel incoherent motion diffusion-weighted imaging, arterial spinning labeling imaging, blood oxygenation level dependent imaging, and three-dimensional MR elastography. ASSESSMENT: Functional variables were measured before and after water challenge. Regions of interest were manually drawn by two investigators (JC and ZZ, with 8- and 5-year experiences in abdominal radiology) in the cortex, the medulla, and the entire kidney. The medulla/cortex ratio was calculated. STATISTICAL TESTS: Paired t-test or Wilcoxon signed rank test; interobserver correlation coefficient; repeatability coefficients; Spearman's correlation; significance level: P < 0.05. RESULTS: Diffusion parameters were only subject to regional variation. R2*, RBF, and renal stiffness (RS) showed regional variation, side variation, and dependence on hydration states. For each side and hydration state, the cortex showed significantly higher standard apparent diffusion coefficient (sADC), higher true diffusion (D), lower R2*, and lower RS than the medulla. For each region at baseline, the left kidney showed significantly higher R2*, higher RS, and lower renal blood flow (RBF) than the right kidney. For each region and side, RS and RBF increased significantly while R2* decreased significantly after water intake. After introducing the intrinsic regional difference, significantly higher medulla/cortex ratio of RS remained after water intake except for RS@90 Hz in the right kidney. DATA CONCLUSION: Renal multiparametric MRI quantifications were affected by regional variation, side variation, and hydration states. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

QQ-NET - using deep learning to solve quantitative susceptibility mapping and quantitative blood oxygen level dependent magnitude (QSM+qBOLD or QQ) based oxygen extraction fraction (OEF) mapping.

PURPOSE: To improve accuracy and speed of quantitative susceptibility mapping plus quantitative blood oxygen level-dependent magnitude (QSM+qBOLD or QQ) -based oxygen extraction fraction (OEF) mapping using a deep neural network (QQ-NET). METHODS: The 3D multi-echo gradient echo images were acquired in 34 ischemic stroke patients and 4 healthy subjects. Arterial spin labeling and diffusion weighted imaging (DWI) were also performed in the patients. NET was developed to solve the QQ model inversion problem based on Unet. QQ-based OEF maps were reconstructed with previously introduced temporal clustering, tissue composition, and total variation (CCTV) and NET. The results were compared in simulation, ischemic stroke patients, and healthy subjects using a two-sample Kolmogorov-Smirnov test. RESULTS: In the simulation, QQ-NET provided more accurate and precise OEF maps than QQ-CCTV with 150 times faster reconstruction speed. In the subacute stroke patients, OEF from QQ-NET had greater contrast-to-noise ratio (CNR) between DWI-defined lesions and their unaffected contralateral normal tissue than with QQ-CCTV: 1.9 ± 1.3 vs 6.6 ± 10.7 (p = 0.03). In healthy subjects, both QQ-CCTV and QQ-NET provided uniform OEF maps. CONCLUSION: QQ-NET improves the accuracy of QQ-based OEF with faster reconstruction.

Temporal clustering, tissue composition, and total variation for mapping oxygen extraction fraction using QSM and quantitative BOLD.

PURPOSE: To improve the accuracy of quantitative susceptibility mapping plus quantitative blood oxygen level-dependent magnitude (QSM+qBOLD or QQ) based mapping of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2 ) using temporal clustering, tissue composition, and total variation (CCTV). METHODS: Three-dimensional multi-echo gradient echo and arterial spin labeling images were acquired from 11 healthy subjects and 33 ischemic stroke patients. Diffusion-weighted imaging (DWI) was also obtained from patients. The CCTV mapping was developed for incorporating tissue-type information into clustering of the previous cluster analysis of time evolution (CAT) and applying total variation (TV). The QQ-based OEF and CMRO2 were reconstructed with CAT, CAT+TV (CATV), and the proposed CCTV, and results were compared using region-of-interest analysis, Kruskal-Wallis test, and post hoc Wilcoxson rank sum test. RESULTS: In simulation, CCTV provided more accurate and precise OEF than CAT or CATV. In healthy subjects, QQ-based OEF was less noisy and more uniform with CCTV than CAT. In subacute stroke patients, OEF with CCTV had a greater contrast-to-noise ratio between DWI-defined lesions and the unaffected contralateral side than with CAT or CATV: 1.9 ± 1.3 versus 1.1 ± 0.7 (P = .01) versus 0.7 ± 0.5 (P < .001). CONCLUSION: The CCTV mapping significantly improves the robustness of QQ-based OEF against noise.

Noninvasive evaluation of diabetic patients with high fasting blood glucose using DWI and BOLD MRI.

PURPOSE: To investigate the renal microstructure changes and hypoxia changes in type 2 diabetic patients and the relationship between them and glucose using both diffusion-weighted imaging (DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI). METHODS: After measuring morning fasting blood glucose, DWI and BOLD MRI were performed in 57 patients with type 2 diabetes mellitus (DM group) and 14 healthy volunteers (NC group). According to the fasting blood glucose levels, diabetic patients were divided into a normoglycemic diabetes group (group A), a less hyperglycemic diabetes group (group B) and a more hyperglycemic diabetes group (group C). The renal parenchymal apparent diffusion coefficient (ADC), renal cortical R2* (CR2*), and medullary R2* (MR2*) were measured, and the R2* ratio between the medulla and cortex (MCR) was calculated. To test for differences in ADC, R2*, and MCR among the four groups, the data were analyzed by separate one-way ANOVAs. The correlations between ADC, R2*, and MCR and the clinical index of renal function were analyzed. RESULTS: Groups B and C had significantly lower ADC values in the renal parenchyma (P = 0.048, 0.002) and significantly higher MR2* and MCR values (P < 0.000, P = 0.001, 0.001, and 0.005, respectively) than the NC group. ADC was negatively correlated with glucose, and MR2*, MCR and glucose showed a weak positive correlation. CONCLUSION: DWI and BOLD may indirectly and qualitatively reflect the kidney microstructure status and hypoxia level of diabetic patients at different blood glucose levels to a certain extent, and possibly guide the clinical treatment of diabetic patients with different blood glucose levels.

Cerebral oxygen extraction fraction (OEF): Comparison of challenge-free gradient echo QSM+qBOLD (QQ) with 15O PET in healthy adults.

We aimed to validate oxygen extraction fraction (OEF) estimations by quantitative susceptibility mapping plus quantitative blood oxygen-level dependence (QSM+qBOLD, or QQ) using 15O-PET. In ten healthy adult brains, PET and MRI were acquired simultaneously on a PET/MR scanner. PET was acquired using C[15O], O[15O], and H2[15O]. Image-derived arterial input functions and standard models of oxygen metabolism provided quantification of PET. MRI included T1-weighted imaging, time-of-flight angiography, and multi-echo gradient-echo imaging that was processed for QQ. Region of interest (ROI) analyses compared PET OEF and QQ OEF. In ROI analyses, the averaged OEF differences between PET and QQ were generally small and statistically insignificant. For whole brains, the average and standard deviation of OEF was 32.8 ± 6.7% for PET; OEF was 34.2 ± 2.6% for QQ. Bland-Altman plots quantified agreement between PET OEF and QQ OEF. The interval between the 95% limits of agreement was 16.9 ± 4.0% for whole brains. Our validation study suggests that respiratory challenge-free QQ-OEF mapping may be useful for non-invasive clinical assessment of regional OEF impairment.

Cluster analysis of time evolution (CAT) for quantitative susceptibility mapping (QSM) and quantitative blood oxygen level-dependent magnitude (qBOLD)-based oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2 ) mapping.

PURPOSE: To improve the accuracy of QSM plus quantitative blood oxygen level-dependent magnitude (QSM + qBOLD or QQ)-based mapping of the oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2 ) using cluster analysis of time evolution (CAT). METHODS: 3D multi-echo gradient echo and arterial spin labeling images were acquired in 11 healthy subjects and 5 ischemic stroke patients. DWI was also carried out on patients. CAT was developed for analyzing signal evolution over TE. QQ-based OEF and CMRO2 were reconstructed with and without CAT, and results were compared using region of interest analysis and a paired t-test. RESULTS: Simulations demonstrated that CAT substantially reduced noise error in QQ-based OEF. In healthy subjects, QQ-based OEF appeared less noisy and more uniform with CAT than without CAT; average OEF with and without CAT in cortical gray matter was 32.7 ± 4.0% and 37.9 ± 4.5%, with corresponding CMRO2 of 148.4 ± 23.8 and 171.4 ± 22.4 µmol/100 g/min, respectively. In patients, regions of low OEF were confined within the ischemic lesions defined on DWI when using CAT, which was not observed without CAT. CONCLUSION: The cluster analysis of time evolution (CAT) significantly improves the robustness of QQ-based OEF against noise.

Blood Oxygen Level-Dependent Imaging and Intravoxel Incoherent Motion MRI of Early Contrast-Induced Acute Kidney Injury in a Rabbit Model.

BACKGROUND: To evaluate the application of blood oxygenation level-dependent (BOLD)imaging and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) on assessing early contrast-induced acute kidney injury (CIAKI). MATERIALS: Sixty rabbits were randomly chosen to undergo iohexol (1.0, 2.5, and 5.0 [gI/kg], respectively; n = 15 for each group) or saline injection (n = 15). In each group, 6 rabbits underwent MRI at 24 h before injection and after injection of iohexol or saline (1 h and 1, 2, 3, and 4 days); meanwhile, out of the remaining 9 rabbits, 3 were chosen for MRI acquisition, and then they were killed at specific time points (1 h, 1 day, and 3 days, respectively). RESULTS: The strong attenuation of pure molecular diffusion (D), apparent diffusion coefficient (ADC), and perfusion fraction (f) was observed at 1 day, while pseudodiffusion coefficient (D*) showed a significant decrease at 1 h after iohexol injection. A distinct elevation of apparent transverse relaxation rate (R2*) reached the maximum levels on day 1, which was consistent with the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor. ADC, D, and R2* correlated well with histopathological parameters and biochemical parameters. CONCLUSION: BOLD combined with IVIM is effective to monitor renal pathophysiology associated with CIAKI.

Evaluation of iodine contrast-induced acute kidney injury via different injection routes using BOLD-MRI.

OBJECTIVES: The aim of this study was to evaluate and compare the severity of acute kidney injury (AKI) induced by iodine contrast agent injection via the renal artery, ear vein, and femoral artery in a rabbit model. METHODS: Blood oxygenation level-dependent (BOLD) magnetic resonance (MR) scans were performed at 24 h prior to contrast injection and 1, 24, 48, and 72 h after injection. Iodixanol injection dose was 1.0, 1.5, 2.0, and 2.5 g iodine/kg, respectively. Hypoxia-inducible factor-1α (HIF-1α) expression was determined, and the BOLD-MRI parameter R2* was used to express tissue oxygenation. Increases in R2* levels reflect reductions in tissue oxygenation. Analyses including R2* value, dose response, histology, and HIF-1α were conducted. RESULT: Injection of 1.0 g iodine/kg into the left renal artery resulted in significant increases in renal R2* values after 24 h. This was equivalent to the change of R2* after 2.0 g iodine/kg femoral artery injection. Renal injury scores and HIF-1α expression scores were significantly increased at 24 h. The R2* values exhibited a positive linear correlation with histological injury scores. The maximum effects occurred 24 h after iodixanol injection and returned to baseline levels within 72 h. CONCLUSIONS: The renal injury induced by 1.0 g iodine/kg iodixanol through renal artery injection was more significant than that caused by the same dose of femoral artery and auricular vein injection, while similar to that caused by 2.0 g iodine/kg femoral artery injection.

Flow-metabolism uncoupling in patients with asymptomatic unilateral carotid artery stenosis assessed by multi-modal magnetic resonance imaging.

Oxygen extraction (OEF), oxidative metabolism (CMRO2), and blood flow (CBF) in the brain, as well as the coupling between CMRO2 and CBF due to cerebral autoregulation are fundamental to brain's health. We used a clinically feasible MRI protocol to assess impairments of these parameters in the perfusion territories of stenosed carotid arteries. Twenty-nine patients with unilateral high-grade carotid stenosis and thirty age-matched healthy controls underwent multi-modal MRI scans. Pseudo-continuous arterial spin labeling (pCASL) yielded absolute CBF, whereas multi-parametric quantitative blood oxygenation level dependent (mqBOLD) modeling allowed imaging of relative OEF and CMRO2. Both CBF and CMRO2 were significantly reduced in the stenosed territory compared to the contralateral side, while OEF was evenly distributed across both hemispheres similarly in patients and controls. The CMRO2-CBF coupling was significantly different between both hemispheres in patients, i.e. significant interhemispheric flow-metabolism uncoupling was observed in patients compared to controls. Given that CBF and CMRO2 are intimately linked to brain function in health and disease, the proposed easily applicable MRI protocol of pCASL and mqBOLD imaging might serve as a valuable tool for early diagnosis of potentially harmful cerebral hemodynamic and metabolic states with the final aim to select clinically asymptomatic patients who would benefit from carotid revascularization therapy.

Cerebral metabolic rate of oxygen (CMRO2 ) mapping by combining quantitative susceptibility mapping (QSM) and quantitative blood oxygenation level-dependent imaging (qBOLD).

PURPOSE: To map the cerebral metabolic rate of oxygen (CMRO2 ) by estimating the oxygen extraction fraction (OEF) from gradient echo imaging (GRE) using phase and magnitude of the GRE data. THEORY AND METHODS: 3D multi-echo gradient echo imaging and perfusion imaging with arterial spin labeling were performed in 11 healthy subjects. CMRO2 and OEF maps were reconstructed by joint quantitative susceptibility mapping (QSM) to process GRE phases and quantitative blood oxygen level-dependent (qBOLD) modeling to process GRE magnitudes. Comparisons with QSM and qBOLD alone were performed using ROI analysis, paired t-tests, and Bland-Altman plot. RESULTS: The average CMRO2 value in cortical gray matter across subjects were 140.4 ± 14.9, 134.1 ± 12.5, and 184.6 ± 17.9 µmol/100 g/min, with corresponding OEFs of 30.9 ± 3.4%, 30.0 ± 1.8%, and 40.9 ± 2.4% for methods based on QSM, qBOLD, and QSM+qBOLD, respectively. QSM+qBOLD provided the highest CMRO2 contrast between gray and white matter, more uniform OEF than QSM, and less noisy OEF than qBOLD. CONCLUSION: Quantitative CMRO2 mapping that fits the entire complex GRE data is feasible by combining QSM analysis of phase and qBOLD analysis of magnitude.

Combined effects of type 2 diabetes and hypertension associated with cortical thinning and impaired cerebrovascular reactivity relative to hypertension alone in older adults.

OBJECTIVE: Type 2 diabetes mellitus is characterized by metabolic dysregulation in the form of hyperglycemia and insulin resistance and can have a profound impact on brain structure and vasculature. The primary aim of this study was to identify brain regions where the combined effects of type 2 diabetes and hypertension on brain health exceed those of hypertension alone. A secondary objective was to test whether vascular impairment and structural brain measures in this population are associated with cognitive function. RESEARCH DESIGN AND METHODS: We enrolled 18 diabetic participants with hypertension (HTN + T2DM, 7 women, 71.8 ± 5.6 years) and 22 participants with hypertension only (HTN, 12 women, 73.4 ± 6.2 years). Cerebrovascular reactivity (CVR) was assessed using blood oxygenation level dependent (BOLD) MRI during successive breath holds. Gray matter structure was evaluated using cortical thickness (CThk) measures estimated from T1-weighted images. Analyses of cognitive and blood data were also performed. RESULTS: Compared to HTN, HTN + T2DM had decreased CVR and CThk in a spatially overlapping region of the right occipital lobe (P < 0.025); CVR group differences were more expansive and included bilateral occipito-parietal areas (P < 0.025). Whereas CVR showed no significant associations with measures of cognitive function (P > 0.05), CThk in the right lingual gyrus ROI and regions resulting from a vertex-wise analysis (including posterior cingulate, precuneus, superior and middle frontal, and middle and inferior temporal regions (P < 0.025) were associated with executive function. CONCLUSIONS: Individuals with T2DM and HTN showed decreased CVR and CThk compared to age-matched HTN controls. This study identifies brain regions that are impacted by the combined effects of comorbid T2DM and HTN conditions, with new evidence that the corresponding cortical thinning may contribute to cognitive decline.