Level-dependent Magnetic Resonance Imaging Research Articles

Considerations for implanting speech brain computer interfaces based on functional magnetic resonance imaging

Objective. Brain-computer interfaces (BCIs) have the potential to reinstate lost communication faculties. Results from speech decoding studies indicate that a usable speech BCI based on activity in the sensorimotor cortex (SMC) can be achieved using subdurally implanted electrodes. However, the optimal characteristics for a successful speech implant are largely unknown. We address this topic in a high field blood oxygenation level dependent functional magnetic resonance imaging (fMRI) study, by assessing the decodability of spoken words as a function of hemisphere, gyrus, sulcal depth, and position along the ventral/dorsal-axis. Approach. Twelve subjects conducted a 7T fMRI experiment in which they pronounced 6 different pseudo-words over 6 runs. We divided the SMC by hemisphere, gyrus, sulcal depth, and position along the ventral/dorsal axis. Classification was performed on in these SMC areas using multiclass support vector machine (SVM). Main results. Significant classification was possible from the SMC, but no preference for the left or right hemisphere, nor for the precentral or postcentral gyrus for optimal word classification was detected. Classification while using information from the cortical surface was slightly better than when using information from deep in the central sulcus and was highest within the ventral 50% of SMC. Confusion matrices where highly similar across the entire SMC. An SVM-searchlight analysis revealed significant classification in the superior temporal gyrus and left planum temporale in addition to the SMC. Significance. The current results support a unilateral implant using surface electrodes, covering the ventral 50% of the SMC. The added value of depth electrodes is unclear. We did not observe evidence for variations in the qualitative nature of information across SMC. The current results need to be confirmed in paralyzed patients performing attempted speech.

Linking renal hypoxia and oxidative stress in chronic kidney disease: Based on clinical subjects and animal models.

This study aims to explore the relationships between renal function, hypoxia, and oxidative stress in chronic kidney disease (CKD). Seventy-six non-dialysis patients with CKD stages 1-5 and eight healthy subjects were included in the clinical research. They were divided into three groups: healthy subjects, CKD stages 1-3, and CKD stages 4-5. In the animal study, 16 rat models of CKD were established through 5/6 renal ablation/infarction (A/I) surgery, and 8 normal rats were split into 3 groups: Sham, CKD, and losartan groups. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) was used to measure cortical and medullary T2* values (COT2* and MET2*) in all subjects and rats to evaluate renal oxygenation. Biochemical indicators were used to assess renal function and antioxidant capacity. Furthermore, the effects of losartan on renal fibrosis, hypoxia, and oxidative stress were examined using immunoblotting, colorimetric, and fluorometric assays. The results demonstrated significant positive associations between COT2* and MET2* with estimated glomerular filtration rate (eGFR). Patients with CKD stages 4-5 showed significantly lower serum superoxide dismutase (SOD) levels, which also had positive correlations with eGFR, COT2*, and MET2*. Furthermore, losartan treatment resulted in improved renal function and fibrosis, leading to increased levels of COT2*, MET2*, and SOD levels in 5/6 A/I rats. This was accompanied by reduced levels of hypoxia-inducible factor-1 alpha (HIF-1α) and malondialdehyde. Furthermore, losartan restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and suppressed the expression of Kelch-like ECH-associated protein 1 (Keap1) in 5/6 A/I kidneys. The study indicates that decline in renal oxygenation and antioxidant capacity is associated with the severity of renal failure in CKD. Losartan can potentially alleviate renal hypoxia and oxidative stress in the treatment of CKD via Keap1-Nrf2/HO-1 pathway.

Magnetic resonance imaging-based approaches for detecting the efficacy of combining therapy following VEGFR-2 and PD-1 blockade in a colon cancer model

BackgroundAngiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model.MethodsThe C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points.ResultsThe combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P < 0.001), indicating the capability of BOLD-MRI to evaluate tumor hypoxia. In addition, the D value of IVIM-DWI is closely related to tumor cell proliferation, apoptosis, and infiltration of lymphocytes. The D value was highly correlated with Ki-67 (r = − 0.792, P < 0.001), TUNEL (r = 0.910, P < 0.001) and CD8a (r = 0.918, P < 0.001).ConclusionsThe combination of VEGFR-2 inhibitors with PD-1 immunotherapy shows a synergistic anti-tumor effect on the mouse colon cancer model. IVIM-DWI and BOLD-MRI are expected to be used as non-invasive approaches to provide imaging-based evidence for tumor response detection and efficacy evaluation.

The differential regulation of placenta trophoblast bisphosphoglycerate mutase in fetal growth restriction: preclinical study in mice and observational histological study of human placenta.

Fetal growth restriction (FGR) is a pregnancy complication in which a newborn fails to achieve its growth potential, increasing the risk of perinatal morbidity and mortality. Chronic maternal gestational hypoxia, as well as placental insufficiency are associated with increased FGR incidence; however, the molecular mechanisms underlying FGR remain unknown. Pregnant mice were subjected to acute or chronic hypoxia (12.5% O2) resulting in reduced fetal weight. Placenta oxygen transport was assessed by blood oxygenation level dependent (BOLD) contrast magnetic resonance imaging (MRI). The placentae were analyzed via immunohistochemistry and in situ hybridization. Human placentae were selected from FGR and matched controls and analyzed by immunohistochemistry (IHC). Maternal and cord sera were analyzed by mass spectrometry. We show that murine acute and chronic gestational hypoxia recapitulates FGR phenotype and affects placental structure and morphology. Gestational hypoxia decreased labyrinth area, increased the incidence of red blood cells (RBCs) in the labyrinth while expanding the placental spiral arteries (SpA) diameter. Hypoxic placentae exhibited higher hemoglobin-oxygen affinity compared to the control. Placental abundance of Bisphosphoglycerate mutase (BPGM) was upregulated in the syncytiotrophoblast and spiral artery trophoblast cells (SpA TGCs) in the murine gestational hypoxia groups compared to the control. Hif1α levels were higher in the acute hypoxia group compared to the control. In contrast, human FGR placentae exhibited reduced BPGM levels in the syncytiotrophoblast layer compared to placentae from healthy uncomplicated pregnancies. Levels of 2,3 BPG, the product of BPGM, were lower in cord serum of human FGR placentae compared to control. Polar expression of BPGM was found in both human and mouse placentae syncytiotrophoblast, with higher expression facing the maternal circulation. Moreover, in the murine SpA TGCs expression of BPGM was concentrated exclusively in the apical cell side, in direct proximity to the maternal circulation. This study suggests a possible involvement of placental BPGM in maternal-fetal oxygen transfer, and in the pathophysiology of FGR. This work was supported by the Weizmann Krenter Foundation and the Weizmann - Ichilov (Tel Aviv Sourasky Medical Center) Collaborative Grant in Biomedical Research, by the Minerva Foundation, by the ISF KillCorona grant 3777/19.

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

BackgroundTo 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).MethodsThe 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.ResultsThe 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).ConclusionsThe 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.

Pathological Factors Affecting the R2* Values of the Kidney in Blood Oxygenation Level-dependent MR Imaging: A Retrospective Study.

Despite the usefulness of blood oxygenation level-dependent (BOLD) MRI in assessing glomerulonephritis activity, its relationship with histological findings remains unclear. Because glomerulonephritis presents multiple complex injury patterns, analysis of each pattern is essential. We aimed to elucidate the relationship between the histological findings of the kidney and BOLD MRI findings in mesangial proliferative glomerulonephritis. Children under 16 years of age diagnosed with mesangial proliferative glomerulonephritis by kidney biopsy at our university hospital between January 2013 and September 2022 were included in this study. Cortical and medullary spin relaxation rate (R2*) values were measured using BOLD MRI at 3T within two weeks before and after the kidney biopsy. The R2* values, including the fluctuations with low-dose oxygen administration, were retrospectively examined in relation to the cortical (mesangial proliferation, endothelial cell proliferation, crescent, sclerosis, and fibrosis) and medullary findings (fibrosis). Sixteen times kidney biopsies were performed for glomerulonephritis during the study period, and one patient was excluded because of comorbidities; the remaining 14 patients included six boys with a mean age of 11.9 ± 3.5 years at the BOLD examination. None of the patients had medullary fibrosis. Among the kidney tissue parameters, only sclerosis showed a significant correlation with R2* values: medulla with R2* values under atmospheric pressure (r = 0.53, P < 0.05) and cortex with the rate of change in R2* values with low-dose oxygen administration (r = -0.57, P < 0.03). In the multiple regression analysis, only sclerosis was an independent contributor to the change in R2* values with oxygen administration in the cortex (regression coefficient -0.109, P < 0.05). Since the R2* values reflect histological changes in the kidney, BOLD MRI may facilitate the evaluation of mesangial proliferative glomerulonephritis, potentially reducing the patient burden.

The relationships between hippocampal cerebrovascular reactivity, hippocampal volume, and episodic memory in healthy ageing

AbstractBackgroundCerebrovascular biomarkers such as cerebrovascular reactivity (CVR) have previously been associated with episodic memory. However, the relationship between memory and regional CVR within the hippocampus is not well studied. Moreover, whether this association is affected by hippocampal volume remains to be investigated. This study investigated the associations between hippocampal physiology, structure, and memory in ageing.MethodData from 104 participants (Age: Mean = 77±4.9 years) of the ongoing Oxford Heart and Brain Study was analysed for this study. CVR was assessed by a compensatory change in the blood oxygenation level dependent magnetic resonance imaging (MRI) signal in response to a 5% CO2 challenge, hippocampus volume was measured by structural MRI, and episodic memory was assessed with the Hopkins Verbal Learning Test Revised (HVLT‐R).ResultMean hippocampal CVR decreased with age (β = ‐0.004, p = 0.006). Mean hippocampal CVR was positively associated with mean hippocampal volume (β = 0.11, p = 0.010), and this association was driven by the left hippocampus after correcting for age and sex. Higher hippocampal CVR was also associated with better performance on the HVLT (β = 13.8, p = 0.035). This association was fully mediated by hippocampal volume, suggesting a path from cerebrovascular reactivity to episodic memory (Sobel’s z = 2.16, p = 0.030, see Figure 1).ConclusionThis study presents novel findings showing that hippocampal CVR was associated with episodic memory, and this association was mediated by hippocampal volume. This suggests a pathway by which impairments in hippocampal CVR are associated with worse episodic memory via smaller hippocampal volumes.

Generalized Calibrated BOLD fMRI for the Relationship between Cerebral Metabolism and Hypertensive Status

AbstractBackgroundElevated blood pressure levels during mid‐life have been found to be associated with an increased susceptibility to developing dementia later in life, particularly vascular dementia. Quantitative imaging biomarkers, such as Oxygen Extraction Fraction (OEF) and Cerebral Metabolism Rate of Oxygen (CMRO2), can be indicators of impaired cerebral metabolism. Calibrated Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) is a multi‐parametric approach utilizing hyperoxic and hypercapnic gas challenges (Figure 1). The impact of hypertension on OEF and CMRO2 has been investigated.MethodA cohort of 84 participants was recruited from the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core (Table 1). Among all the covariates, participants with prediabetes and diabetes were considered diabetic, and those who exhibited high blood pressure or were using medication to manage hypertension were classified as hypertensive. The MRI was conducted using a 3T Siemens Skyra MRI scanner with a 32‐channel head coil. Dynamic Pseudocontinuous Arterial Spin Labeling (PCASL) was used to acquire cerebral blood flow (CBF) and BOLD images during respiratory challenges with an end‐tidal forcing system. The ROI values in the frontal lobe, temporal lobe, parietal lobe, and occipital lobe regions were chosen. The correlation between hypertensive status and OEF and CMRO2 in the ROI was analyzed with a linear mixed model, with covariates of age, sex, cognitive status, APOE genotype, diabetic status, and hypertensive status.ResultA negative correlation was found between CBF, OEF, and CMRO2 with hypertensive status in frontal lobe region (Figure 2). Statistical significance was observed for OEF and CMRO2 (p = 0.049 and p = 0.028, respectively), indicating the potential influence of hypertensive status on these biomarkers.ConclusionThe study concludes that there is a significant negative association between hypertensive status and both OEF and CMRO2, particularly in the frontal lobe region. The observed reduction in OEF and CMRO2 is not solely due to decreased CBF, but rather complex and multifactorial processes involving vascular remodeling and altered oxygen metabolism. Additional research is necessary to fully understand the underlying pathophysiological mechanisms that link hypertension to decreased OEF and CMRO2, particularly in the context of regional specificity.

Assessment of brainstem function and haemodynamics by MRI: challenges and clinical prospects.

MRI offers techniques for non-invasively measuring a range of aspects of brain tissue function. Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used to assess neural activity, based on the brain's haemodynamic response, while arterial spin labelling (ASL) MRI is a non-invasive method of quantitatively mapping cerebral perfusion. Both techniques can be applied to measure cerebrovascular reactivity (CVR), an important marker of the health of the cerebrovascular system. BOLD, ASL and CVR have been applied to study a variety of disease processes and are already used in certain clinical circumstances. The brainstem is a critical component of the central nervous system and is implicated in a variety of disease processes. However, its function is difficult to study using MRI because of its small size and susceptibility to physiological noise. In this article, we review the physical and biological underpinnings of BOLD and ASL and their application to measure CVR, discuss the challenges associated with applying them to the brainstem and the opportunities for brainstem MRI in the research and clinical settings. With further optimisation, functional MRI techniques could feasibly be used to assess brainstem haemodynamics and neural activity in the clinical setting.

COVID-19 during pregnancy could potentially affect placental function

Objective COVID-19 is an ongoing pandemic and has been extensively studied. However, the effects of COVID-19 during pregnancy, particularly on placental function, have not been verified. In this study, we used blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate whether COVID-19 incidence during pregnancy has any lasting effects with respect to placental oxygenation. Methods This is a case-control study, in which eight cases of singleton pregnancies before 30 weeks gestation with COVID-19 mothers were included. Placental oxygenation was evaluated using BOLD-MRI after 32 weeks of gestation. BOLD-MRI was consecutively performed under normoxia (21% O2), hyperoxia (100% O2), and normoxia for 4 min each. Individual placental time–activity curves were evaluated to calculate the peak score (peakΔR2*) and the time from the start of maternal oxygen administration to the time of peakΔR2* (time to peakΔR2*). Eighteen COVID-19-free normal pregnancies from a previous study were used as the control group. Results No significant differences were found between the two groups regarding maternal background, number of days of delivery, birth weight, and placental weight. The parameter peakΔR2* was significantly decreased in the COVID-19 group (8 ± 3 vs. 5 ± 1, p < .001); however, there was no significant difference in time to peakΔR2* (458 ± 74 s vs. 471 ± 33 s, p = .644). Conclusions In this study, BOLD-MRI was used to evaluate placental oxygenation during pregnancy in COVID-19-affected patients. COVID-19 during pregnancy decreased placental oxygenation even post-illness, but had no effect on fetal growth; further investigation of the possible effects of COVID-19 on the fetus and mother is warranted.

Convolutional Neural Networks to Assess Steno-Occlusive Disease Using Cerebrovascular Reactivity.

Cerebrovascular Reactivity (CVR) is a provocative test used with Blood oxygenation level-dependent (BOLD) Magnetic Resonance Imaging (MRI) studies, where a vasoactive stimulus is applied and the corresponding changes in the cerebral blood flow (CBF) are measured. The most common clinical application is the assessment of cerebral perfusion insufficiency in patients with steno-occlusive disease (SOD). Globally, millions of people suffer from cerebrovascular diseases, and SOD is the most common cause of ischemic stroke. Therefore, CVR analyses can play a vital role in early diagnosis and guiding clinical treatment. This study develops a convolutional neural network (CNN)-based clinical decision support system to facilitate the screening of SOD patients by discriminating between healthy and unhealthy CVR maps. The networks were trained on a confidential CVR dataset with two classes: 68 healthy control subjects, and 163 SOD patients. This original dataset was distributed in a ratio of 80%-10%-10% for training, validation, and testing, respectively, and image augmentations were applied to the training and validation sets. Additionally, some popular pre-trained networks were imported and customized for the objective classification task to conduct transfer learning experiments. Results indicate that a customized CNN with a double-stacked convolution layer architecture produces the best results, consistent with expert clinical readings.

Can the apparent transverse relaxation rate (R2*) evaluate the efficacy of concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma? a preliminary experience

BackgroundThe use of the apparent transverse relaxation rate (R2*) in nasopharyngeal carcinoma (NPC) has not been previously reported in the literature. The aim of this study was to investigate the role of the R2* value in evaluating response to concurrent chemoradiotherapy (CCRT) in patients with NPC.MethodsForty-one patients with locoregionally advanced NPC confirmed by pathology were examined by blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) before and after CCRT, and conventional MRI was performed 3 months after the completion of CCRT. All patients were divided into a responding group (RG) and a nonresponding group (NRG), according to MRI findings 3 months after the end of treatment. The R2* values before (R2*preT) and after (R2*postT) CCRT and the ΔR2* (ΔR2*=R2*postT – R2*preT) were calculated in the tumor.ResultsAmong the 41 patients, 26 were in the RG and 15 were in the NRG. There was no statistical difference in the R2*preT between RG and NRG (P = 0.307); however, there were significant differences in R2*postT and ΔR2* (P < 0.001). The area under the curve of R2*postT and ΔR2* for predicting the therapeutic response of NPC was 0.897 and 0.954, respectively, with cutoff values of 40.95 and 5.50 Hz, respectively.ConclusionThe R2* value can be used as a potential imaging indicator to evaluate the therapeutic response of locoregionally advanced NPC.

Quantitative Blood Oxygenation Level Dependent Magnetic Resonance Imaging for Estimating Intra-renal Oxygen Availability Demonstrates Kidneys Are Hypoxemic in Human CKD

Kidney blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) has shown great promise in evaluating relative oxygen availability. This method is quite efficacious in evaluating acute responses to physiological and pharmacologic maneuvers. Its outcome parameter, R2∗ is defined as the apparent spin-spin relaxation rate measured in the presence of magnetic susceptibility differences and it is measured using gradient echo MRI. Although associations between R2∗ and renal function decline have been described, it remains uncertain to what extent R2∗ is a true reflection of tissue oxygenation. This is primarily because of not taking into account the confounding factors, especially fractional blood volume (fBV) in tissue. This case-control study included 7 healthy controls and 6 patients with diabetes and chronic kidney disease (CKD). Using data before and after administration of ferumoxytol, a blood pool MRI contrast media, the fBVs in kidney cortex and medulla were measured. This pilot study independently measured fBV in kidney cortex (0.23 ± 0.03 vs. 0.17 ± 0.03) and medulla (0.36 ± 0.08 vs. 0.25 ± 0.03) in a small number of healthy controls (n= 7) versus CKD (n= 6). These were then combined with BOLD MRI measurements to estimate oxygen saturation of hemoglobin (StO2) (0.87 ± 0.03 vs. 0.72 ± 0.10 in cortex; 0.82 ± 0.05 vs. 0.72 ± 0.06 in medulla) and partial pressure of oxygen in blood (bloodPO2) (55.4 ± 6.5 vs. 38.4 ± 7.6 mmHg in cortex; 48.4 ± 6.2 vs. 38.1 ± 4.5 mmHg in medulla) in control versus CKD. The results for the first time demonstrate that cortex is normoxemic in controls and moderately hypoxemic in CKD. In the medulla, it is mildly hypoxemic in controls and moderately hypoxemic in CKD. Whereas fBV, StO2, and bloodPO2 were strongly associated with estimated glomerular filtration rate (eGFR), R2∗ was not. Our results support the feasibility of quantitatively assessing oxygen availability using noninvasive quantitative BOLD MRI that could be translated to the clinic.

Evaluation of T2-prepared blood oxygenation level dependent functional magnetic resonance imaging with an event-related task: Hemodynamic response function and reproducibility.

T2-prepared (T2prep) blood oxygenation level dependent (BOLD) functional MRI (fMRI) is an alternative fMRI approach developed to mitigate the susceptibility artifacts that are typically observed in brain regions near air-filled cavities, bleeding and calcification, and metallic objects in echo-planar-imaging (EPI) based fMRI images. Here, T2prep BOLD fMRI was evaluated in an event-related paradigm for the first time. Functional experiments were performed using gradient-echo (GRE) EPI, spin-echo (SE) EPI, and T2prep BOLD fMRI during an event-related visual task in 10 healthy human subjects. Each fMRI method was performed with a low (3.4 × 3.4 × 4 mm3) and a high (1.5 mm isotropic) spatial resolution on 3T and a high resolution (1.5 mm isotropic) on 7T. Robust activation were detected in the visual cortex with all three fMRI methods. In each group of fMRI scans (3T low resolution, 3T high resolution, and 7T high resolution), GRE EPI showed the highest signal change (ΔS/S), largest full-width-at-half-maximum (FWHM) and longest time-to-peak (TTP) extracted from the hemodynamic response functions (HRF), indicating substantial signal contribution from large draining veins which have longer response times than microvessels. In contrast, T2prep BOLD showed the lowest ΔS/S, smallest FWHM, and shortest TTP, suggesting that T2prep BOLD may have a purer T2-weighted BOLD contrast that is more sensitive to microvessels compared to GRE/SE EPI BOLD. This trend was more obvious in fMRI scans performed with a lower spatial resolution on a lower field (3T with a 3.4 × 3.4 × 4 mm3 voxel). Scan-rescan reproducibility in the same subjects was comparable among the three fMRI methods. The results from the current study are expected to be useful to establish T2prep BOLD as a useful alternative fMRI approach for event-related fMRI in brain regions with large susceptibility artifacts.

Cerebrovascular reactivity measurements using 3T BOLD MRI and a fixed inhaled CO2 gas challenge: Repeatability and impact of processing strategy.

Introduction: Cerebrovascular reactivity (CVR) measurements using blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) are commonly used to assess the health of cerebral blood vessels, including in patients with cerebrovascular diseases; however, evidence and consensus regarding reliability and optimal processing are lacking. We aimed to assess the repeatability, accuracy and precision of voxel- and region-based CVR measurements at 3 T using a fixed inhaled (FI) CO2 stimulus in a healthy cohort. Methods: We simulated the effect of noise, delay constraints and voxel- versus region-based analysis on CVR parameters. Results were verified in 15 healthy volunteers (28.1±5.5years, female: 53%) with a test-retest MRI experiment consisting of two CVR scans. CVR magnitude and delay in grey matter (GM) and white matter were computed for both analyses assuming a linear relationship between the BOLD signal and time-shifted end-tidal CO2 (EtCO2) profile. Results: Test-retest repeatability was high [mean (95% CI) inter-scan difference: -0.01 (-0.03, -0.00) %/mmHg for GM CVR magnitude; -0.3 (-1.2,0.6) s for GM CVR delay], but we detected a small systematic reduction in CVR magnitude at scan 2 versus scan 1, accompanied by a greater EtCO2 change [±1.0 (0.4,1.5) mmHg] and lower heart rate [-5.5 (-8.6,-2.4] bpm]. CVR magnitude estimates were higher for voxel- versus region-based analysis [difference in GM: ±0.02 (0.01,0.03) %/mmHg]. Findings were supported by simulation results, predicting a positive bias for voxel-based CVR estimates dependent on temporal contrast-to-noise ratio and delay fitting constraints and an underestimation for region-based CVR estimates. Discussion: BOLD CVR measurements using FI stimulus have good within-day repeatability in healthy volunteers. However, measurements may be influenced by physiological effects and the analysis protocol. Voxel-based analyses should be undertaken with care due to potential for systematic bias; region-based analyses are more reliable in such cases.

Effects of alfaxalone, propofol and isoflurane on cerebral blood flow and cerebrovascular reactivity to carbon dioxide in dogs: A pilot study.

Propofol total intravenous anesthesia is a common choice to anesthetize patients with increased intracranial pressure, reducing cerebral blood flow while maintaining cerebrovascular reactivity to CO2. Propofol and alfaxalone are commonly used for total intravenous anesthesia in dogs, but the effects of alfaxalone on cerebral blood flow and cerebrovascular reactivity to CO2 are unknown. Our hypothesis was that alfaxalone would not be significantly different to propofol, while isoflurane would increase cerebral blood flow and decrease cerebrovascular reactivity to CO2. Six healthy hound dogs were evaluated in this randomized crossover trial. Dogs were anesthetized with 7.5mg/kg propofol, 3mg/kg alfaxalone or 8% sevoflurane, mechanically ventilated and maintained with propofol (400µg/kg/min), alfaxalone (150µg/kg/min) or 1.7% end-tidal isoflurane, respectively, with one week washout between treatments. Cerebral blood flow and cerebrovascular reactivity to CO2 during hypercapnic and hypocapnic challenges were measured using arterial spin labelling and blood oxygen level-dependent magnetic resonance imaging sequences, respectively. Median (interquartile range, IQR) normocapnic cerebral blood flow was significantly lower (P=0.016) with alfaxalone compared to isoflurane, in the whole brain 15.39mL/min/100g (14.90-19.90mL/min/100g) vs. 34.10mL/min/100g (33.35-43.17mL/min/100g), the grey matter 14.57mL/min/100g (13.66-18.72mL/min/100g) vs. 32.37mL/min/100g (31.03-42.99mL/min/100g), the caudal brain 15.47mL/min/100g (13.37-21.45mL/min/100g) vs. 36.85mL/min/100g (32.50-47.18mL/min/100g) and the temporal lobe grey matter 18.80mL/min/100g (15.89-20.84mL/min/100g) vs. 43.32 (36.07-43.58mL/min/100g). Median (IQR) hypocapnic cerebrovascular reactivity to CO2 was significantly higher (P=0.016) for alfaxalone compared to isoflurane 8.85%S/mm Hg (6.92-10.44%S/mm Hg) vs. 3.90%S/mm Hg (3.80-4.33%S/mm Hg). Alfaxalone maintained lower cerebral blood flow and higher hypocapnic cerebrovascular reactivity to CO2 than isoflurane.

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 r > 0.4, p 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 (β2-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 “Conclusion: The decline of renal oxygenation reflected on T2* values, especially in cortex, may be an effective diagnostic marker for early detection of CKD.

The value of magnetic resonance blood oxygen level-dependent imaging in evaluating the efficacy of advanced cervical cancer combined with radiotherapy and chemotherapy.

Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) is an imaging method used to analyze oxygenation status of the tumor. To investigate the feasibility of BOLD-MRI in evaluating the efficacy of advanced cervical cancer combined with radiotherapy and chemotherapy. This prospective study included 85 patients with advanced cervical cancer who received BOLD-MRI examination before and after concurrent chemoradiotherapy from October 2020 to December 2021. To investigate the changes of baseline R2* values and △R2* values of cervical cancers before and after treatment. 29 cases were complete response, 34 cases were partial response, and 22 cases showed progression. The baseline R2* values of the tumors were lower than that of the normal cervical muscle (P < 0.0001). After oxygen stimulation, the baseline R2* values of the tumors decreased (P = 0.012). After treatment, the baseline R2* values of the tumors increased (P = 0.007), and the dynamic △R2* values of the tumors decreased (P = 0.025). The baseline R2* value of the complete response was the highest (P = 0.000), the dynamic △R2* value of the complete response was the lowest (P = 0.017). BOLD-MRI can evaluate the efficacy of concurrent chemoradiotherapy for advanced cervical cancer.

Evaluating renal iron overload in diabetes mellitus by blood oxygen level-dependent magnetic resonance imaging: a longitudinal experimental study

BackgroundIron overload plays a critical role in the pathogenesis of diabetic nephropathy. Non-invasive evaluation of renal iron overload in diabetes in the management and intervention of diabetic nephropathy is of great significance. This study aimed to explore the feasibility of blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in evaluating renal iron overload in diabetes using a rabbit model.MethodsThe rabbits were randomly divided into control, iron-overload (I), diabetes (D), and diabetes with iron-overload (DI) groups (each n = 19). The diabetes models were generated by injecting intravenous alloxan solution, and the iron-overload models were generated by injecting intramuscular iron-dextran. BOLD MRI was performed immediately (week 0) and at week 4, 8, and 12 following modeling. The differences in renal cortex (CR2*) and outer medulla R2* (MR2*) and the ratio of MR2*–CR2* (MCR) across the different time points were compared.ResultsIron was first deposited in glomeruli in the I group and in proximal tubular cells in renal cortex in the D group. In the DI group, there was iron deposition in both glomeruli and proximal tubular cells at week 4, and the accumulation increased subsequently. The degree of kidney injury and iron overload was more severe in the DI group than those in the I and D groups at week 12. At week 8 and 12, the CR2* and MR2* in the DI group were higher than those in the I and D groups (all P < 0.05). The MCR in the I, D, and DI groups decreased from week 0 to 4 (all P < 0.001), and that in the I group increased from week 8 to 12 (P = 0.034). CR2* and MR2* values displayed different trends from week 0–12. Dynamic MCR curves in the D and DI groups were different from that in the I group.ConclusionIt presents interactions between diabetes and iron overload in kidney injury, and BOLD MRI can be used to evaluate renal iron overload in diabetes.

Cyclic changes in T2* relaxometry of human uterus during the menstrual cycle using BOLD MR imaging

PurposeTo evaluate dynamic changes of T2* values within the endometrium, junctional zone and myometrium during the menstrual cycle using blood oxygen level-dependent (BOLD) magnetic resonance imaging. MethodVolunteers underwent MRI scans on menstrual phase, ovulatory phase and luteal phase, including T2-weighted imaging and BOLD MR imaging. Multi-gradient-recalled echo (MGRE) sequence was used to obtain BOLD MR images. T2* values of different uterine layers, including endometrium, junctional zone and myometrium, on sagittal images were analyzed quantitatively. ResultsTwenty-four subjects calculated T2* values successfully. The T2* values of each zonal structure during menstruation were significantly lower than those during ovulatory phase (P < 0.05) and luteal phase (P < 0.001). The T2* value of junctional zone was significantly lower than that of the myometrium over all three menstrual phases (P = 0.000, menstrual; P = 0.000, ovulatory; P = 0.001, luteal). The mean T2* value in endometrium during the ovulatory phase was the highest of the uterine zones over menstrual cycle. During menstrual phase, there was no statistical difference between endometrium and junctional zone (P > 0.05). Conversely, the comparison of the T2* values between endometrium and myometrium, junctional zone and myometrium both showed significant difference (P = 0.000). The mean T2* values within endometrium during ovulatory phase and luteal phase were significantly higher than those within junctional zone and myometrium (P < 0.05). ConclusionsCyclic changes of T2* values in each zonal structure of the uterus were revealed during the menstrual cycle by means of BOLD technique, which may be potentially beneficial in investigating dysmenorrhea, guiding assisted reproductive technologies and monitoring hypoxia in gynecological tumors.