Effect of inhaled oxygen level on dynamic glucose-enhanced MRI in mouse brain.

PURPOSE: To investigate the effect of inhaled oxygen level on dynamic glucose enhanced (DGE) MRI in mouse brain tissue and CSF at 3 T. METHODS: DGE data of brain tissue and CSF from mice under normoxia or hyperoxia were acquired in independent and interleaved experiments using on-resonance variable delay multi-pulse (onVDMP) MRI. A bolus of 0.15 mL filtered 50% D-glucose was injected through the tail vein over 1 min during DGE acquisition. MRS was acquired before and after DGE experiments to confirm the presence of D-glucose. RESULTS: A significantly higher DGE effect under normoxia than under hyperoxia was observed in brain tissue (p = 0.0001 and p = 0.0002 for independent and interleaved experiments, respectively), but not in CSF (p > 0.3). This difference is attributed to the increased baseline MR tissue signal under hyperoxia induced by a shortened T1 and an increased BOLD effect. When switching from hyperoxia to normoxia without glucose injection, a signal change of ˜3.0% was found in brain tissue and a signal change of ˜1.5% was found in CSF. CONCLUSIONS: DGE signal was significantly lower under hyperoxia than that under normoxia in brain tissue, but not in CSF. The reason is that DGE effect size of brain tissue is affected by the baseline signal, which could be influenced by T1 change and BOLD effect. Therefore, DGE experiments in which the oxygenation level is changed from baseline need to be interpreted carefully.

Passive hyperthermia alters the resting-state functional connectivity of mouse brain.

PURPOSE: To investigate how passive hyperthermia affect the resting-state functional brain activity based on an acute mouse model after heat stress exposure. MATERIALS AND METHODS: Twenty-eight rs-fMRI data of C57BL/6J male mice which weighing about 24 ∼ 29 g and aged 12 ∼ 16 weeks were collected. The mice in the hyperthermia group (HT, 40 °C ± 0.5 °C, 40 min) were subjected to passive hyperthermia before the anesthesia preparation for scanning. While the normal control group (NC) was subjected to normothermia condition (NC, 20 °C ± 2 °C, 40 min). After data preprocessing, we performed independent component analysis (ICA) and region of interested (ROI)-ROI functional connectivity (FC) analyses on the data of both HT (n = 13) and NC (n = 15). RESULTS: The group ICA analysis showed that the HT and the NC both included 11 intrinsic connectivity networks (ICNs), and can be divided into four types of networks: the cortical network (CN), the subcortical network (SN), the default mode network (DMN), and cerebellar networks. CN and SN belongs to sensorimotor network. Compared with NC, the functional network organization of ICNs in the HT was altered and the overall functional intensity was decreased. Furthermore, 13 ROIs were selected in CN, SN, and DMN for further ROI-ROI FC analysis. The ROI-ROI FC analysis showed that passive hyperthermia exposure significantly reduced the FC strength in the overall brain represented by CN, SN, DMN of mice. CONCLUSION: Prolonged exposure to high temperature has a greater impact on the overall perception and cognitive level of mice, which might help understand the relationship between neuronal activities and physiological thermal sensation and regulation as well as behavioral changes.

Value of blood oxygenation level-dependent magnetic resonance imaging in early evaluation of the response and prognosis of esophageal squamous cell carcinoma treated with definitive chemoradiotherapy: a preliminary study.

BACKGROUND: To find a useful hypoxia non-invasive biomarker for evaluating early treatment response and prognosis to definitive chemoradiotherapy (dCRT) in patients with esophageal squamous cell carcinoma (ESCC), using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). METHODS: The R2* values were obtained pre- and 2-3 weeks post-dCRT in 28 patients with ESCC using BOLD MRI. Independent samples t-test (normality) or Mann-Whitney U test (non-normality) was used to compare the differences of R2*-related parameters between the complete response (CR) and the non-CR groups. Diagnostic performance of parameters in predicting response was tested with receiver operating characteristic (ROC) curve analysis. The 3-year overall survival (OS) was evaluated using Kaplan Meier curve, log rank test, and Cox proportional hazards regression analysis. RESULTS: The post-R2*, ∆R2*, and ∆%R2* in the CR group were significantly higher than those in the non-CR group (P = 0.002, 0.003, and 0.006, respectively). The R2*-related parameters showed good prediction of tumor response, with AUC ranging from 0.813 to 0.829. The 3-year OS rate in patients with ∆R2* >-7.54 s- 1 or CR were significantly longer than those with ∆R2* ≤ -7.54 s- 1 (72.37% vs. 0.00%; Hazard ratio, HR = 0.196; 95% confidence interval, 95% CI = 0.047-0.807; P = 0.024) or non-CR (76.47% vs. 29.27%; HR = 0.238, 95% CI = 0.059-0.963; P = 0.044). CONCLUSIONS: The preliminary results demonstrated that the R2* value might be a useful hypoxia non-invasive biomarker for assessing response and prognosis of ESCC treated with dCRT. BOLD MRI might be used as a potential tool for evaluating tumor oxygenation metabolism, which is routinely applied in clinical practice and beneficial to clinical decision-making. A large sample size was needed for further follow-up studies to confirm the findings.

Insomnia disorder characterized by probabilistic metastable substates using blood-oxygenation-level-dependent (BOLD) phase signals.

PURPOSE: From a clinical point of view, how to force a transition from insomnia brain state to healthy brain state by external driven stimulation is of great interest. This needs to define brain state of insomnia disorder as metastable substates. The current study was to identify recurrent substates of insomnia disorder in terms of probability of occurrence, lifetime, and alternation profiles by using leading eigenvector dynamics analysis (LEiDA) method. METHODS: We enrolled 32 patients with insomnia disorder and 30 healthy subjects. We firstly obtained the BOLD phase coherence matrix from Hilbert transform of BOLD signals and then extracted all the leading eigenvectors from the BOLD phase coherence matrix for all subjects across all time points. Lastly, we clustered the leading eigenvectors using a k-means clustering algorithm to find the probabilistic metastable substates (PMS) and calculate the probability of occurrence and associated lifetime for substates. RESULTS: The resulting 3 clusters were optimal for brain state of insomnia disorder and healthy brain state, respectively. The occurred probabilities of the PMS were significantly different between the patients with insomnia disorder and healthy subjects, with 0.51 versus 0.44 for PMS-1 (p < 0.001), 0.25 versus 0.27 for PMS-2 (p = 0.051), and 0.24 versus 0.29 for PMS-3 (p < 0.001), as well as the lifetime (in TR) of 36.65 versus 33.15 for PMS-1 (p = 0.068), 14.36 versus 15.43 for PMS-2 (p = 0.117), and 14.80 versus 16.34 for PMS-3 (p = 0.042). The values of the diagonal of the transition matrix were much higher than the probabilities of switching states, indicating the metastable nature of substates. CONCLUSION: The resulted probabilistic metastable substates hint the characteristic brain dynamics of insomnia disorder. The results may lay a foundation to help determine how to force a transition from insomnia brain state to healthy brain state by external driven stimulation.

Shen Shuai II recipe improves renal hypoxia to attenuate renal injury in 5/6 renal ablation/infarction rats and effect evaluation using blood oxygenation level-dependent functional magnetic resonance imaging.

Background: Renal hypoxia plays a key role in the progression of chronic kidney disease (CKD). Shen Shuai II Recipe (SSR) has shown good results in the treatment of CKD as a common herbal formula. This study aimed to explore the effect of SSR on renal hypoxia and injury in CKD rats. Methods: Twenty-five Wistar rats underwent 5/6 renal ablation/infarction (A/I) surgery were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + losartan (LOS), and 5/6 (A/I) + SSR groups. Another eight normal rats were used as the Sham group. After 8-week corresponding interventions, blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) was performed to evaluate renal oxygenation in all rats, and biochemical indicators were used to measure kidney and liver function, hemoglobin, and proteinuria. The expression of fibrosis and hypoxia-related proteins was analyzed using immunoblotting examination. Results: Renal oxygenation, evaluated by BOLD-fMRI as cortical and medullary T2* values (COT2* and MET2*), was decreased in 5/6 (A/I) rats, but increased after SSR treatment. SSR also downregulated the expression of hypoxia-inducible factor-1α (HIF-1α) in 5/6 (A/I) kidneys. With the improvement of renal hypoxia, renal function and fibrosis were improved in 5/6 (A/I) rats, accompanied by reduced proteinuria. Furthermore, the COT2* and MET2* were significantly positively correlated with the levels of creatinine clearance rate (Ccr) and hemoglobin, but negatively associated with the levels of serum creatinine (SCr), blood urea nitrogen (BUN), serum cystatin C (CysC), serum uric acid (UA), 24-h urinary protein (24-h Upr), and urinary albumin:creatinine ratio (UACR). Conclusion: The degree of renal oxygenation reduction is correlated with the severity of renal injury in CKD. SSR can improve renal hypoxia to attenuate renal injury in 5/6 (A/I) rats of CKD.

Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease-related cognitive decline: Multi-site validation in the MarkVCID Consortium.

INTRODUCTION: Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis. METHODS: We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes. RESULTS: CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function. DISCUSSION: The predefined hypothesis on the association between CVR and a global cognitive score was validated in three independent analysis sites, providing support for CVR as a biomarker in VCID. HIGHLIGHTS: This study measured a novel functional index of small arteries referred to as cerebrovascular reactivity (CVR). CVR was positively associated with global cognition in older adults. This finding was observed in three independent cohorts at three sites. Our statistical analysis plan was predefined before beginning data collection.

Cerebral oxygen metabolism from MRI susceptibility.

This article provides an overview of MRI methods exploiting magnetic susceptibility properties of blood to assess cerebral oxygen metabolism, including the tissue oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2). The first section is devoted to describing blood magnetic susceptibility and its effect on the MRI signal. Blood circulating in the vasculature can have diamagnetic (oxyhemoglobin) or paramagnetic properties (deoxyhemoglobin). The overall balance between oxygenated and deoxygenated hemoglobin determines the induced magnetic field which, in turn, modulates the transverse relaxation decay of the MRI signal via additional phase accumulation. The following sections of this review then illustrate the principles underpinning susceptibility-based techniques for quantifying OEF and CMRO2. Here, it is detailed whether these techniques provide global (OxFlow) or local (Quantitative Susceptibility Mapping - QSM, calibrated BOLD - cBOLD, quantitative BOLD - qBOLD, QSM+qBOLD) measurements of OEF or CMRO2, and what signal components (magnitude or phase) and tissue pools they consider (intravascular or extravascular). Validations studies and potential limitations of each method are also described. The latter include (but are not limited to) challenges in the experimental setup, the accuracy of signal modeling, and assumptions on the measured signal. The last section outlines the clinical uses of these techniques in healthy aging and neurodegenerative diseases and contextualizes these reports relative to results from gold-standard PET.

Physiological modeling of the BOLD signal and implications for effective connectivity: A primer.

In this primer, I provide an overview of the physiological processes that contribute to the observed BOLD signal (i.e., the generative biophysical model), including their time course properties within the framework of the physiologically-informed dynamic causal modeling (P-DCM). The BOLD signal is primarily determined by the change in paramagnetic deoxygenated hemoglobin, which results from combination of changes in oxygen metabolism, and cerebral blood flow and volume. Specifically, the physiological origin of the so-called BOLD signal "transients" will be discussed, including the initial overshoot, steady-state activation and the post-stimulus undershoot. I argue that incorrect physiological assumptions in the generative model of the BOLD signal can lead to incorrect inferences pertaining to both local neuronal activity and effective connectivity between brain regions. In addition, I introduce the recent laminar BOLD signal model, which extends P-DCM to cortical depths-resolved BOLD signals, allowing for laminar neuronal activity to be determined using high-resolution fMRI data.

Abnormal voxel-mirrored homotopic connectivity in first-episode, drug-naïve patients with obsessive-compulsive disorder.

Prior studies suggest that obsessive-compulsive disorder (OCD) can cause both anatomical and functional variations in the brain, but to date, altered functional synchronization between two functional hemispheres remains unclear in OCD patients. Voxel-mirrored homotopic connectivity (VMHC) is defined as the temporal correlation of spontaneous low-frequency blood oxygenation level-dependent signal fluctuations across mirror regions of hemisphere revealing the homotopic connectivity between each voxel in one hemisphere and its mirrored counterpart in the contralateral hemisphere. To investigate the alterations of brain regional function and VMHC in patients with OCD, the current study enrolled 103 OCD patients and 118 healthy controls, undergoing resting-state functional magnetic resonance imaging. Compared to healthy controls (HCs), patients had decreased VMHC in bilateral cerebellum, lingual and fusiform gyrus; bilateral paracentral lobule, pre and postcentral gyrus; and bilateral superior and middle temporal gyrus, putamen and bilateral precuneus without global signal regression. And we found mostly similar results after regressing global signals; apart from the regions mentioned above, decreased in bilateral cuneus and calcarine was also showed. Furthermore, the mean VMHC values of the left cerebellum were negatively correlated with the obsession scores (ρ = -.204, π = .039). The decreased values in right fusiform and putamen were negatively correlated with duration of disease (ρ = -.205, π = .038; ρ = -.196, π = .047). We confirmed a significant VMHC reduction in OCD patients in broad areas. Our findings suggest that the patients tend to disconnect information exchange across hemispheres.

Spatial distribution of hand-grasp motor task activity in spinal cord functional magnetic resonance imaging.

Upper extremity motor paradigms during spinal cord functional magnetic resonance imaging (fMRI) can provide insight into the functional organization of the cord. Hand-grasping is an important daily function with clinical significance, but previous studies of similar squeezing movements have not reported consistent areas of activity and are limited by sample size and simplistic analysis methods. Here, we study spinal cord fMRI activation using a unimanual isometric hand-grasping task that is calibrated to participant maximum voluntary contraction (MVC). Two task modeling methods were considered: (1) a task regressor derived from an idealized block design (Ideal) and (2) a task regressor based on the recorded force trace normalized to individual MVC (%MVC). Across these two methods, group motor activity was highly lateralized to the hemicord ipsilateral to the side of the task. Activation spanned C5-C8 and was primarily localized to the C7 spinal cord segment. Specific differences in spatial distribution are also observed, such as an increase in C8 and dorsal cord activity when using the %MVC regressor. Furthermore, we explored the impact of data quantity and spatial smoothing on sensitivity to hand-grasp motor task activation. This analysis shows a large increase in number of active voxels associated with the number of fMRI runs, sample size, and spatial smoothing, demonstrating the impact of experimental design choices on motor activation.

Modelling the depth-dependent VASO and BOLD responses in human primary visual cortex.

Functional magnetic resonance imaging (fMRI) using a blood-oxygenation-level-dependent (BOLD) contrast is a common method for studying human brain function noninvasively. Gradient-echo (GRE) BOLD is highly sensitive to the blood oxygenation change in blood vessels; however, the spatial signal specificity can be degraded due to signal leakage from activated lower layers to superficial layers in depth-dependent (also called laminar or layer-specific) fMRI. Alternatively, physiological variables such as cerebral blood volume using the VAscular-Space-Occupancy (VASO) contrast have shown higher spatial specificity compared to BOLD. To better understand the physiological mechanisms such as blood volume and oxygenation changes and to interpret the measured depth-dependent responses, models are needed which reflect vascular properties at this scale. For this purpose, we extended and modified the "cortical vascular model" previously developed to predict layer-specific BOLD signal changes in human primary visual cortex to also predict a layer-specific VASO response. To evaluate the model, we compared the predictions with experimental results of simultaneous VASO and BOLD measurements in a group of healthy participants. Fitting the model to our experimental data provided an estimate of CBV change in different vascular compartments upon neural activity. We found that stimulus-evoked CBV change mainly occurs in small arterioles, capillaries, and intracortical arteries and that the contribution from venules and ICVs is smaller. Our results confirm that VASO is less susceptible to large vessel effects compared to BOLD, as blood volume changes in intracortical arteries did not substantially affect the resulting depth-dependent VASO profiles, whereas depth-dependent BOLD profiles showed a bias towards signal contributions from intracortical veins.

Noninvasive Assessment of the Renal Function, Oxford Classification and Prognostic Risk Stratification of IgAN by Using Intravoxel Incoherent Motion Diffusion-Weighted Imaging and Blood Oxygenation Level-Dependent MRI.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Oxford classification including mesangial hypercellularity (M), endothelial hypercellularity (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T), and crescent (C) were recommended to predict the prognosis of IgAN. PURPOSE: To explore whether multiparametric magnetic resonance imaging (MRI) can be applied to assess the renal function, Oxford classification, and risk of progression to end-stage kidney disease within 5 years of IgAN. STUDY TYPE: Prospective. POPULATION: A total of 46 patients with pathologically confirmed IgAN and 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: A 3-T, blood oxygenation level-dependent (BOLD)-MRI, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: Two radiologists measured the cortex and medulla T2*, apparent diffusion coefficient (ADC), true diffusion (Dt), pseudo-diffusion (Dp), perfusion fraction (fp). All participants were divided into three groups: group 1, healthy volunteers; group 2, patients with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 ; group 3, patients with eGFR <60 mL/min/1.73 m2 . Or two groups: group A, 5-year risk scores ≤10% and group B, 5-year risk scores >10%. STATISTICAL TESTS: Intraclass correlation coefficient, one-way analysis of variance, least-significant difference, Student's t-test, Pearson product-moment correlation, Spearman's rank correlation, and receiver operating characteristics (ROC) with the area under the curve (AUC). A P value <0.05 was considered statistically significant. RESULTS: Except for cortical Dp, all other MRI parameters showed significant differences between group 1 and group 2. None of the MRI parameters showed a significant correlation with M, E, or C scores. Cortical T2*, Dt, fp, and medullary Dt and fp showed low-to-moderate significant correlations with S scores. Except for cortical and medullary Dp, all other MRI parameters were significantly correlated with T scores. Cortical Dt showed the largest AUC for differentiating group A from group B (AUC = 0.927) and T0 from T1/T2 (AUC = 0.963). DATA CONCLUSION: Imaging by IVIM-DWI and BOLD-MRI could facilitate noninvasive assessment of the renal function, Oxford classification, and prognostic risk of IgAN patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

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.

Correlation of Renal Oxygenation with Renal Function in Chronic Kidney Disease: A Preliminary Prospective Study.

INTRODUCTION: Chronic hypoxia is prevalent in chronic kidney disease (CKD), and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) provides noninvasive evaluation of renal oxygenation. This study aimed to explore the correlation of renal oxygenation evaluated by BOLD-MRI with renal function. METHODS: 97 non-dialysis patients with CKD stages 1-5 and healthy volunteers (HVs) were recruited in the study, all participants without diabetes. Based on their estimated glomerular filtration rate (eGFR), the patients were divided into two groups: CKD stages 1-3 (CKD 1-3) and CKD stages 4-5 (CKD 4-5). We measured cortical and medullary T2* (COT2* and MET2*) values in all participants by BOLD-MRI. Physiological indices were also recorded and compared among three groups. Correlation of T2* values with clinical characteristics was determined. RESULTS: The COT2* values were significantly higher than MET2* values in all participants. The COT2* and MET2* values of three groups were ranked as HV > CKD 1-3> CKD 4-5 (p < 0.0001). There were positive correlations between the COT2* values, MET2* values and eGFR, hemoglobin (r > 0.4, p < 0.01). The 24-h urinary protein (24-h Upr) showed weak correlation with the COT2* value (rs = -0.2301, p = 0.0265) and no correlation with the MET2* value (p > 0.05). Urinary microprotein, including urinary alpha1-microglobulin, urinary beta2-microglobulin (ß2-MG), and urinary retinol-binding protein (RBP), showed strong correlation with COT2* and MET2* values. According to the analysis of receiver operating characteristic curve, the optimal cut-points between HV and CKD 1-3 were "<61.17 ms" (sensitivity: 91.23%, specificity: 100%) for COT2* values and "<35.00 ms" (sensitivity: 77.19%, specificity: 100%) for MET2* values, whereas COT2* values ("<47.34 ms"; sensitivity: 90.00%, specificity: 92.98%) and MET2* values ("<25.09 ms"; sensitivity: 97.50%, specificity: 80.70%) between CKD 1-3 and CKD 4-5. CONCLUSION: The decline of renal oxygenation reflected on T2* values, especially in cortex, may be an effective diagnostic marker for early detection of CKD.

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.

Contrast-agent-free state-of-the-art MRI on cerebral small vessel disease-part 1. ASL, IVIM, and CVR.

Cerebral small vessel disease (cSVD), a common cause of stroke and dementia, is traditionally considered the small vessel equivalent of large artery occlusion or rupture that leads to cortical and subcortical brain damage. Microvessel endothelial dysfunction can also contribute to it. Brain imaging, including MRI, is useful to show the presence of lesions of several types, although the association between conventional MRI measures and clinical features of cSVD is not always concordant. We assessed the additional contribution of contrast-agent-free, state-of-the-art MRI techniques such as arterial spin labeling (ASL), diffusion tensor imaging, functional MRI, and intravoxel incoherent motion (IVIM) applied to cSVD in the existing literature. We performed a review following the PICO Worksheet and Search Strategy, including original papers in English, published between 2000 and 2022. For each MRI method, we extracted information about their contributions, in addition to those established with traditional MRI methods and related information about the origins, pathology, markers, and clinical outcomes in cSVD. This paper presents the first part of the review, which includes 37 studies focusing on ASL, IVIM, and cerebrovascular reactivity (CVR) measures. In general, they have shown that, in addition to white matter hyperintensities, alterations in other neuroimaging parameters such as blood flow and CVR also indicate the presence of cSVD. Such quantitative parameters were also related to cSVD risk factors. Therefore, they are promising, noninvasive tools to explore questions that have not yet been clarified about this clinical condition. However, protocol standardization is essential to increase their clinical use.

Future of kidney imaging: Functional magnetic resonance imaging and kidney disease progression.

INTRODUCTION: Chronic kidney disease (CKD) which is a common cause of death has an increasing trend, but there is no established approach for predicting CKD progression yet. Functional magnetic resonance imaging (fMRI) studies such as blood oxygenation level-dependent MRI (BOLD-MRI), diffusion-weighted MRI (DWI-MRI), diffusion-tensor MRI (DTI-MRI) and arterial spin labelling MRI (ASL-MRI) are rising methods for the assessment of kidney functions in native and transplanted kidneys as well as the estimation of CKD progression. METHODS: Systematic literature review was performed through the Embase (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), PubMed/Medline and Web of Science databases, and studies investigating the role of fMRI methods assessing kidney functions in native and transplanted kidneys, as well as the value of fMRI methods to predict CKD progression, were included. Working mechanisms, advantages and limitations of the fMRI modalities were reviewed, and three studies investigating the role of fMRI studies in kidney functions were analysed. RESULTS AND CONCLUSION: BOLD-MRI signal was found to be inversely correlated with annual eGFR change, and DWI/ADC (apparent diffusion coefficient map) values were shown to be correlated with annual eGFR decline. fMRI methods which are currently used for other systems can be utilized to provide more detailed information about kidney functions, and doctors should be ready to interpret kidney MRIs.

Introducing a New Biomarker Named R2*-BOLD-MRI Parameter to Assess Treatment Response in Osteosarcoma.

BACKGROUND: While histologic response to neoadjuvant chemotherapy (NChT) is the major prognostic factor for osteosarcoma treatment, evaluating that response is difficult. PURPOSE: To evaluate the feasibility of the blood oxygen level-dependent (BOLD) technique to assess the response to NChT. STUDY TYPE: Prospective. POPULATION: Twelve patients with osteosarcoma undergoing NChT. FIELD STRENGTH/SEQUENCE: 3 T; T2*-weighted BOLD, dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) (b values of 0, 400, and 1400 seconds/mm2 ) sequences. ASSESSMENT: Examination was performed before treatment (first), after each cycle of treatment (second and third). At each time point, spin dephasing rates (R2*) from BOLD magnetic resonance imaging (MRI), parameters from DCE-MRI (volume transfer constant [Ktrans ], reflux rate [kep ], volume fraction of the extravascular extracellular matrix [ve ], and blood plasma volume [vp ]), and the apparent diffusion coefficient (ADC) from DW-MRI were measured. STATISTICAL TESTS: Wilcoxon's signed rank test, Spearman's correlation coefficient (ρ) were used. A P-value of <0.05 was considered statistically significant. RESULTS: The difference and relative difference of the R2* values between the first/third MRIs in the extraosseous portion were statistically significant. Only the differences in the kep values between the first/second and between the first/third MRIs in the extraosseous portion were significant. The differences in the ADCs in the extraosseous and osseous portions were not statistically significant (P = 0.151, P = 0.733 each in extraosseous portion and P = 0.569, P = 0.129 each in osseous portion). The relative difference in R2* values in the extraosseous portion between the first/third MRI (ρ = 0.706) was significantly better correlated with the pathologic grade than those of kep and ADC over the same period (ρ = 0.286 and ρ = -0.091, respectively). DATA CONCLUSION: The R2* from the BOLD MRI technique could be a useful biomarker for evaluating treatment response in osteosarcoma treated with NchT. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Noninvasive Evaluation of Renal Hypoxia by Multiparametric Functional MRI in Early Diabetic Kidney Disease.

BACKGROUND: Renal hypoxia, which caused by a mismatch between oxygen delivery and oxygen demand, may be the primary pathophysiological pathway driving diabetic kidney disease (DKD). Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) could detect hypoxia, but can be limited in distinguishing increased oxygen consumption or decreased blood supply. PURPOSE: To explore multiparametric functional MRI in evaluating mechanism of the hypoxia changes in early stage of DKD. STUDY TYPE: Prospective. ANIMAL MODEL: Thirty-five New Zealand White rabbits were divided into control group (n = 5) and alloxan-induced diabetes mellitus (DM) groups (DM3 group: n = 15, DM7 group: n = 15). FIELD STRENGTH/SEQUENCE: 3 T MRI/BOLD, arterial spin labeling (ASL), and asymmetric spin-echo (ASE). ASSESSMENT: The renal oxygenation level (R2*), renal blood flow (RBF), and oxygen extraction fraction (OEF) were evaluated by BOLD, ASL, and ASE MRI, respectively. The regions of interest were manually drawn including cortex, outer stripes of outer medulla (OS), and inner stripes of outer medulla (IS). STATISTICAL TESTS: Analysis of variance, independent-sample t-test, and paired-sample t-test were applied for comparisons among groups, between groups, and within the same group. P < 0.05 was considered statistically significant. RESULTS: All renal regions of DM3 group at Day 3 after DM induction showed significantly higher R2* and OEF values compared to baseline. The RBF values showed no statistically significant difference (P = 0.62, 0.76, 0.09 in cortex, OS, and IS, respectively). For DM7 group at Day 7, R2*, OEF, and RBF values showed no statistically significant difference compared to baseline (P = 0.06, 0.05, 0.06 of R2*; 0.70, 0.64, 0.68 of OEF; and 0.33, 0.58, 0.48 of RBF in cortex, OS, and IS, respectively). DATA CONCLUSION: BOLD MRI could detect renal hypoxia in early stage of DKD rabbit model, which was mainly revealed by increased oxygen consumption, but not affected by renal blood flow change. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1.

Oxygen extraction fraction (OEF) assesses cerebral oxygen metabolism of deep gray matter in patients with pre-eclampsia.

OBJECTIVES: The objective of this study was to compare oxygen extraction fraction (OEF) values in the deep gray matter (GM) of pre-eclampsia (PE) patients, pregnant healthy controls (PHCs), and non-pregnant healthy controls (NPHCs) to explore their brain oxygen metabolism differences in GM. METHODS: Forty-seven PE patients, forty NPHCs, and twenty-one PHCs were included. Brain OEF values were computed from quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude (QSM + qBOLD = QQ)-based mapping. One-way ANOVA was used to compare mean OEF values in the three groups. The area under the curve of the mean OEF value in each region of interest was estimated using a receiver operating characteristic curve analysis. RESULTS: We found that the mean OEF values in the thalamus, putamen, caudate nucleus, pallidum, and substantia nigra were significantly different in these three groups (F = 5.867, p = 0.004; F = 5.142, p = 0007; F = 6.158, p = 0.003; F = 6.319, p = 0.003; F = 5.491, p = 0.005). The mean OEF values for these 5 regions were higher in PE patients than in NPHCs and in PHCs (p < 0.05). The AUC of these ROIs ranged from 0.673 to 0.692 (p < 0.01) and cutoff values varied from 35.1 to 36.6%, indicating that the OEF values could discriminate patients with and without PE. Stepwise multivariate analysis revealed that the OEF values correlated with hematocrit in pregnant women (r = 0.353, p = 0.003). CONCLUSION: OEF values in the brains of pregnant women can be measured in clinical practice using QQ-based OEF mapping for noninvasive assessment of hypertensive disorders. KEY POINTS: • Pre-eclampsia is a hypertensive disorder associated with abnormalities in brain oxygen extraction. • Oxygen extraction fraction (OEF) is an indicator of brain tissue viability and function. QQ-based mapping of OEF is a new MRI technique that can noninvasively quantify brain oxygen metabolism. • OEF values in the brains of pregnant women can be measured for noninvasive assessment of hypertensive disorders in clinical practice.