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Background: Recent clinical studies suggest protective effects of SGLT2 inhibitors on kidney disease outcome. Chronic hypoxia has a critical role in kidney disease development, thus we speculated that canagliflozin, an SGLT2 inhibitor, can improve kidney oxygenation. Methods: A single-arm study was conducted to investigate the effects of canagliflozin on T2* value, which reflects oxygenation level, in patients with type 2 diabetes (T2D) using repeated blood oxygenation level-dependent MRI (BOLD MRI) examinations. Changes in cortical T2* frombefore (Day 0) to after single-dose treatment (Day 1) and after five consecutive treatments (Day 5) were evaluated using 12-layer concentric objects (TLCO) and region of interest (ROI) methods. Results: In the full analysis set (n=14 patients), the TLCO method showed no change of T2* with canagliflozin treatment, whereas the ROI method found that cortical T2* was significantly increased on Day 1 but not on Day 5. Sensitivity analysis using TLCO in 13 well-measured patients showed that canagliflozin significantly increased T2* on Day 1 with no change on Day 5, whereas a significant improvement in cortical T2* following canagliflozin treatment was found on both Day 1 and 5 using ROI. Conclusions: Short-term canagliflozin treatment may improve cortical oxygenation and lead to better kidney outcomes in patients with T2D. [ABSTRACT FROM AUTHOR]

Objectives: T2*‐weighted magnetic resonance imaging (MRI) sequences have been identified as non‐invasive tools with which to study placental oxygenation in vivo. This study aimed to use these to investigate both static and dynamic responses to hyperoxia of the normal placenta across gestation. Methods: We conducted a single‐center prospective study including 52 uncomplicated pregnancies. Two T2*‐weighted sequences (T2* relaxometry) were performed, one before and one after maternal hyperoxia. The distribution of placental T2* values was modeled by fitting a gamma probability density function (T2* ~Γαβ), describing the structure of the histogram using the mean T2* value, the shape parameter (α) and the rate (β). A dynamic acquisition (blood‐oxygen‐level‐dependent (BOLD) MRI) was also performed before and during maternal oxygen supply, until placental oxygen saturation had been achieved. The signal change over time was modeled using a sigmoid function, to determine the intensity of enhancement (ΔBOLD (% with respect to baseline)), a temporal variation coefficient (λ (min–1), controlling the slope of the curve) and the maximum steepness (Vmax (% of placental enhancement/min)). Results: The histogram analysis of the T2* values in normoxia showed a whole‐placenta variation, with a decreasing linear trend in the mean T2* value (Pearson's correlation coefficient (R) = −0.83 (95% CI, −0.9 to −0.71), P < 0.001), along with an increasingly peaked and narrower distribution of T2* values with advancing gestation. After maternal hyperoxia, the mean T2* ratios (mean T2*hyperoxia/mean T2*baseline) were positively correlated with gestational age, while the other histogram parameters remained stable, suggesting a translation of the histogram towards higher values with a similar appearance after maternal hyperoxia. ΔBOLD showed a non‐linear increase across gestation. Conversely, λ showed an inverted trend across gestation, with a weaker correlation (R = −0.33 (95% CI, −0.58 to −0.02), P = 0.04, R2 = 0.1). As a combination of ΔBOLD and λ, the changes in Vmax throughout gestation were influenced mainly by the changes in ΔBOLD and showed a positive non‐linear correlation with gestational age. Conclusions: Our results suggest that the decrease in the T2* placental signal as gestation progresses does not reflect placental dysfunction. The BOLD dynamic signal change is representative of a free‐diffusion model of oxygenation and highlights the increasing differences in oxygen saturation between mother and fetus as gestation progresses (ΔBOLD) and in the placental permeability to oxygen (λ). © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

The brain relies on an effective clearance mechanism to remove metabolic waste products for the maintenance of homeostasis. Recent studies have focused on elucidating the forces that drive the motion of cerebrospinal fluid (CSF), responsible for removal of these waste products. We demonstrate that vascular responses evoked using controlled manipulations of partial pressure of carbon dioxide (PaCO2) levels, serve as an endogenous driver of CSF clearance from the brain. To demonstrate this, we retrospectively surveyed our database, which consists of brain metastases patients from whom blood oxygen level‐dependent (BOLD) images were acquired during targeted hypercapnic and hyperoxic respiratory challenges. We observed a correlation between CSF inflow signal around the fourth ventricle and CO2‐induced changes in cerebral blood volume. By contrast, no inflow signal was observed in response to the nonvasoactive hyperoxic stimulus, validating our measurements. Moreover, our results establish a link between the rate of the hemodynamic response (to elevated PaCO2) and peritumoral edema load, which we suspect may affect CSF flow, consequently having implications for brain clearance. Our expanded perspective on the factors involved in neurofluid flow underscores the importance of considering both cerebrovascular responses, as well as the brain mechanical properties, when evaluating CSF dynamics in the context of disease processes. [ABSTRACT FROM AUTHOR]

Objectives: Blood‐oxygen‐level‐dependent (BOLD) magnetic resonance imaging (MRI) facilitates the non‐invasive in‐vivo evaluation of placental oxygenation. The aims of this study were to identify and quantify a relative BOLD effect in response to hyperoxia in the human placenta and to compare it between pregnancies with and those without fetal growth restriction (FGR). Methods: This was a prospective multicenter study (NCT02238301) of 19 pregnancies with FGR (estimated fetal weight (EFW) on ultrasound < 5th centile) and 75 non‐FGR pregnancies (controls) recruited at two centers in Paris, France. Using a 1.5‐Tesla MRI system, the same multi‐echo gradient‐recalled echo (GRE) sequences were performed at both centers to obtain placental T2* values at baseline and in hyperoxic conditions. The relative BOLD effect was calculated according to the equation 100 × (hyperoxic T2* − baseline T2*)/baseline T2*. Baseline T2* values and relative BOLD effect were compared according to EFW (FGR vs non‐FGR), presence/absence of Doppler anomalies and birth weight (small‐for‐gestational age (SGA) vs non‐SGA). Results: We observed a relative BOLD effect in response to hyperoxia in the human placenta (median, 33.8% (interquartile range (IQR), 22.5–48.0%)). The relative BOLD effect did not differ significantly between pregnancies with and those without FGR (median, 34.4% (IQR, 24.1–48.5%) vs 33.7% (22.7–47.4%); P = 0.95). Baseline T2* Z‐score adjusted for gestational age at MRI was significantly lower in FGR pregnancies compared with non‐FGR pregnancies (median, −1.27 (IQR, −4.87 to −0.10) vs 0.33 (IQR, −0.81 to 1.02); P = 0.001). Baseline T2* Z‐score was also significantly lower in those pregnancies that subsequently delivered a SGA neonate (n = 23) compared with those that delivered a non‐SGA neonate (n = 62) (median, −0.75 (IQR, −3.48 to 0.29) vs 0.35 (IQR, −0.79 to 1.05); P = 0.01). Conclusions: Our study confirms a BOLD effect in the human placenta and that baseline T2* values are significantly lower in pregnancies with FGR. Further studies are needed to evaluate whether such parameters may detect placental insufficiency before it has a clinical impact on fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

BackgroundRecent clinical studies suggest protective effects of SGLT2 inhibitors on kidney disease outcome. Chronic hypoxia has a critical role in kidney disease development, thus we speculated that canagliflozin, an SGLT2 inhibitor, can improve kidney oxygenation.MethodsA single-arm study was conducted to investigate the effects of canagliflozin on T2* value, which reflects oxygenation level, in patients with type 2 diabetes (T2D) using repeated blood oxygenation level-dependent MRI (BOLD MRI) examinations. Changes in cortical T2* from before (Day 0) to after single-dose treatment (Day 1) and after five consecutive treatments (Day 5) were evaluated using 12-layer concentric objects (TLCO) and region of interest (ROI) methods.ResultsIn the full analysis set (n=14 patients), the TLCO method showed no change of T2* with canagliflozin treatment, whereas the ROI method found that cortical T2* was significantly increased on Day 1 but not on Day 5. Sensitivity analysis using TLCO in 13 well-measured patients showed that canagliflozin significantly increased T2* on Day 1 with no change on Day 5, whereas a significant improvement in cortical T2* following canagliflozin treatment was found on both Day 1 and 5 using ROI.ConclusionsShort-term canagliflozin treatment may improve cortical oxygenation and lead to better kidney outcomes in patients with T2D.

Objective: Dynamic BOLD MRI with cuff compression, inducing ischemia and post-occlusive hyperemia in skeletal muscle, has been pointed out as a potential diagnostic tool to assess peripheral limb perfusion. The objective was to explore the robustness of this technique and its sensitivity to the occlusion duration. Materials and methods: BOLD images were acquired at 3 T in 14 healthy volunteers. T 2 ∗ -imaging with 5- and 1.5-min occlusions were acquired and several semi-quantitative BOLD parameters were derived from ROI-based T 2 ∗ -time curves. Differences in parameters from the two different occlusion durations were evaluated in the gastrocnemius and soleus muscles using non-parametrical tests. Intra- and inter-scan repeatability were evaluated with coefficient of variation. Results: Longer occlusion duration resulted in an increased hyperemic signal effect yielding significantly different values (p < 0.05) in gastrocnemius for all parameters describing the hyperemic response, and in soleus for two of these parameters. Specifically, 5-min occlusion yielded steeper hyperemic upslope in gastrocnemius (41.0%; p < 0.05) and soleus (59.7%; p = 0.03), shorter time to half peak in gastrocnemius (46.9%; p = 0.00008) and soleus (33.5%; p = 0.0003), and shorter time to peak in gastrocnemius (13.5%; p = 0.02). Coefficients of variation were lower than percentage differences that were found significant. Discussion: Findings show that the occlusion duration indeed influences the hyperemic response and thus should play a part in future methodological developments. [ABSTRACT FROM AUTHOR]

Background: Percutaneous-transluminal renal angioplasty (PTRA) and stenting aim to halt the progression of kidney disease in patients with renal artery stenosis (RAS), but its outcome is often suboptimal. We hypothesized that a model incorporating markers of renal function and oxygenation extracted using radiomics analysis of blood oxygenation-level dependent (BOLD)-MRI images may predict renal response to PTRA in swine RAS. Materials and Methods: Twenty domestic pigs with RAS were scanned with CT and BOLD MRI before and 4 weeks after PTRA. Stenotic (STK) and contralateral (CLK) kidney volume, blood flow (RBF), and glomerular filtration rate (GFR) were determined, and BOLD-MRI R2 * maps were generated before and after administration of furosemide, a tubular reabsorption inhibitor. Radiomics features were extracted from pre-PTRA BOLD maps and Robust features were determined by Intraclass correlation coefficients (ICC). Prognostic models were developed to predict post-PTRA renal function based on the baseline functional and BOLD-radiomics features, using Lasso-regression for training, and testing with resampling. Results: Twenty-six radiomics features passed the robustness test. STK oxygenation distribution pattern did not respond to furosemide, whereas in the CLK radiomics features sensitive to oxygenation heterogeneity declined. Radiomics-based model predictions of post-PTRA GFR (r = 0.58, p = 0.007) and RBF (r = 0.68; p = 0.001) correlated with actual measurements with sensitivity and specificity of 92% and 67%, respectively. Models were unsuccessful in predicting post-PTRA systemic measures of renal function. Conclusions: Several radiomics features are sensitive to cortical oxygenation patterns and permit estimation of post-PTRA renal function, thereby distinguishing subjects likely to respond to PTRA and stenting.

Background: Crossed cerebellar diaschisis (CCD) refers to depressions in perfusion and metabolism within the cerebellar hemisphere contralateral to supratentorial disease. Prior investigation into CCD in cerebrovascular reactivity (CVR) has been limited to terminal CVR estimations (CVRend). We recently have demonstrated the presence of unsustained CVR maxima (CVRmax) using dynamic CVR analysis, offering a fully dynamic characterization of CVR to hemodynamic stimuli. Purpose: To investigate CCD in CVRmax from dynamic blood oxygen level‐dependent (BOLD) MRI, by comparison with conventional CVRend estimation. Study Type: Retrospective. Population: A total of 23 patients (median age: 51 years, 10 females) with unilateral chronic steno‐occlusive cerebrovascular disease, without prior knowledge of CCD status. Field Strength/Sequence: A 3‐T, T1‐weighted magnetization‐prepared rapid gradient‐echo (MPRAGE) and acetazolamide‐augmented BOLD imaging performed with a gradient‐echo echo‐planar imaging (EPI) sequence. Assessment: A custom denoising pipeline was used to generate BOLD‐CVR time signals. CVRend was established using the last minute of the BOLD response relative to the first‐minute baseline. Following classification of healthy versus diseased cerebral hemispheres, CVRmax and CVRend were calculated for bilateral cerebral and cerebellar hemispheres. Three independent observers evaluated all data for the presence of CCD. Statistical Tests: Pearson correlations for comparing CVR across hemispheres, two‐proportion Z‐tests for comparing CCD prevalence, and Wilcoxon signed‐rank tests for comparing median CVR. The level of statistical significance was set at P ≤ 0.05. Results: CCD‐related changes were observed on both CVRend and CVRmax maps, with all CCD+ cases identifiable by inspection of either map. Diseased cerebral and contralateral cerebellar hemispheric CVR correlations in CCD+ patients were stronger when using CVRend (r = 0.728) as compared to CVRmax (r = 0.676). CVR correlations between healthy cerebral hemispheres and contralateral cerebellar hemispheres were stronger for CVRmax (r = 0.739) than for CVRend (r = 0.705). Data Conclusion: CCD‐related alterations could be observed in CVR examinations. Conventional CVRend may underestimate CVR and could exaggerate CCD. Evidence Level: 4. Technical Efficacy: Stage 3. [ABSTRACT FROM AUTHOR]

Congenital anemias, including sickle cell anemia and thalassemia, are associated with cerebral tissue hypoxia and heightened stroke risks. Recent works in sickle cell disease mouse models have suggested that hyperoxia respiratory challenges can identify regions of the brain having chronic tissue hypoxia. Therefore, this work investigated differences in hyperoxic response and regional cerebral oxygenation between anemic and healthy subjects. A cohort of 38 sickle cell disease subjects (age 22 ± 8 years, female 39%), 25 non-sickle anemic subjects (age 25 ± 11 years, female 52%), and 31 healthy controls (age 25 ± 10 years, female 68%) were examined. A hyperoxic gas challenge was performed with concurrent acquisition of blood oxygen level-dependent (BOLD) MRI and near-infrared spectroscopy (NIRS). In addition to hyperoxia-induced changes in BOLD and NIRS, global measurements of cerebral blood flow, oxygen delivery, and cerebral metabolic rate of oxygen were obtained and compared between the three groups. Regional BOLD changes were not able to identify brain regions of flow limitation in chronically anemic patients. Higher blood oxygen content and tissue oxygenation were observed during hyperoxia gas challenge. Both control and anemic groups demonstrated lower blood flow, oxygen delivery, and metabolic rate compared to baseline, but the oxygen metabolism in anemic subjects were abnormally low during hyperoxic exposure. These results indicated that hyperoxic respiratory challenge could not be used to identify chronically ischemic brain. Furthermore, the low hyperoxia-induced metabolic rate suggested potential negative effects of prolonged oxygen therapy and required further studies to evaluate the risk for hyperoxia-induced oxygen toxicity and cerebral dysfunction. [ABSTRACT FROM AUTHOR]

Harmonization of acquisition and analysis protocols is an important step in the validation of BOLD MRI as a renal biomarker. This harmonization initiative provides technical recommendations based on a consensus report with the aim to move towards standardized protocols that facilitate clinical translation and comparison of data across sites. We used a recently published systematic review paper, which included a detailed summary of renal BOLD MRI technical parameters and areas of investigation in its supplementary material, as the starting point in developing the survey questionnaires for seeking consensus. Survey data were collected via the Delphi consensus process from 24 researchers on renal BOLD MRI exam preparation, data acquisition, data analysis, and interpretation. Consensus was defined as ≥ 75% unanimity in response. Among 31 survey questions, 14 achieved consensus resolution, 12 showed clear respondent preference (65-74% agreement), and 5 showed equal (50/50%) split in opinion among respondents. Recommendations for subject preparation, data acquisition, processing and reporting are given based on the survey results and review of the literature. These technical recommendations are aimed towards increased inter-site harmonization, a first step towards standardization of renal BOLD MRI protocols across sites. We expect this to be an iterative process updated dynamically based on progress in the field.

Renal hypoxia has recently been implicated as a key contributor and indicator of various glomerular diseases. As such, monitoring changes in renal oxygenation in these disorders may provide an early diagnostic advantage that could prevent potential adverse outcomes. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) is an emerging noninvasive technique for assessing renal oxygenation in glomerular disease. Although BOLD MRI has produced promising initial results for the use in certain renal pathologies, the use of BOLD imaging in glomerular diseases, including primary and secondary nephrotic and nephritic syndromes, is relatively unexplored. Early BOLD studies on primary nephrotic syndrome, nephrotic syndrome secondary to diabetes mellitus, and nephritic syndrome secondary to systemic lupus erythematosus have shown promising results to support its future clinical utility. In this review, we outline the advancements made in understanding the use of BOLD MRI for the assessment, diagnosis, and screening of these pathologies.

Percutaneous-transluminal renal angioplasty (PTRA) and stenting aim to halt the progression of kidney disease in patients with renal artery stenosis (RAS), but its outcome is often suboptimal. We hypothesized that a model incorporating markers of renal function and oxygenation extracted using radiomics analysis of blood oxygenation-level dependent (BOLD)-MRI images may predict renal response to PTRA in swine RAS. Twenty domestic pigs with RAS were scanned with CT and BOLD MRI before and 4 weeks after PTRA. Stenotic (STK) and contralateral (CLK) kidney volume, blood flow (RBF), and glomerular filtration rate (GFR) were determined, and BOLD-MRI R2 * maps were generated before and after administration of furosemide, a tubular reabsorption inhibitor. Radiomics features were extracted from pre-PTRA BOLD maps and Robust features were determined by Intraclass correlation coefficients (ICC). Prognostic models were developed to predict post-PTRA renal function based on the baseline functional and BOLD-radiomics features, using Lasso-regression for training, and testing with resampling. Twenty-six radiomics features passed the robustness test. STK oxygenation distribution pattern did not respond to furosemide, whereas in the CLK radiomics features sensitive to oxygenation heterogeneity declined. Radiomics-based model predictions of post-PTRA GFR (r = 0.58, p = 0.007) and RBF (r = 0.68; p = 0.001) correlated with actual measurements with sensitivity and specificity of 92% and 67%, respectively. Models were unsuccessful in predicting post-PTRA systemic measures of renal function. Several radiomics features are sensitive to cortical oxygenation patterns and permit estimation of post-PTRA renal function, thereby distinguishing subjects likely to respond to PTRA and stenting. [Display omitted] • MR oxygenation maps unveil tissue engagement, and hypoxia susceptibility. • Radiomics mines spatial kidney oxygenation patterns characteristics. • Oxygenation heterogeneity may predict stenting kidney outcomes. • Heterogeneity signals tubular health; grave harm lessens revascularization gains. • Radiomics-guided renal BOLD probes noninvasively into histological tissue damage. [ABSTRACT FROM AUTHOR]

Aim: Primary objective of this study was to compare R2* value of the post-stenotic kidney with contralateral kidney, kidneys of essential hypertensive patients, and healthy subjects using blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) technique. The secondary objective was to study the effect of severity of stenosis and viability of kidneys on R2* value. Methods: We compared 4 groups of kidneys including 92 with renal artery stenosis, 37 normal contralateral kidneys of unilateral renal artery stenosis patients, 62 kidneys of essential hypertensive patients, and 40 kidneys of healthy controls using BOLD MRI. Deoxyhemoglobin level represented by R2* was calculated before and after giving furosemide and was compared among different groups. Results: Baseline means cortical R2* value did not differ between groups. Response to furosemide was reduced in stenotic kidneys as compared to essential hypertensive and healthy control groups (p < 0.001). The mean R2* value of the contralateral normal kidney group was not significantly different from the stenotic group. Baseline R2* value and delta R2* values did not differ between different degrees of stenosis. Higher mean cortical R2* was seen in stenotic kidneys which were small (< 7 cm) in size (24.27 ± 5.65 vs 21.7 ± 3.88; p value 0.02) or with poor corticomedullary differentiation (24.64 ± 5.8 vs 20.74 ± 3.34; p value 0.006) as compared to other stenotic kidneys. Similarly, the delta R2* value was also blunted in these small shrunken kidneys (p value < 0.001). Conclusion: R2* values on BOLD MRI are significantly different between kidneys with and without renal artery stenosis and can potentially also predict the utility of revascularization. [ABSTRACT FROM AUTHOR]

Introduction: A significant number of patients who present with mild symptoms following large-vessel occlusion acute ischemic stroke (LVO-AIS) are currently considered ineligible for EVT. However, they frequently experience neurological deterioration during hospitalization. This study aimed to investigate the association between neurological deterioration and hemodynamic impairment by assessing steal phenomenon derived from blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) in this specific patient cohort., Patients and Methods: From the database of our single-center BOLD-CVR observational cohort study (June 2015-October 2023) we retrospectively identified acute ischemic stroke patients with admission NIHSS < 6, a newly detected large vessel occlusion of the anterior circulation and ineligible for EVT. Neurological deterioration during hospitalization as well as outcome at hospital discharge were rated with NIHSS score. We analyzed the association between these two outcomes and BOLD-CVR-derived steal phenomenon volume through regression analysis. Additionally, we investigated the discriminatory accuracy of steal phenomenon volume for predicting neurological deterioration., Results: Forty patients were included in the final analysis. Neurological deterioration occurred in 35% of patients. In the regression analysis, a strong association between steal phenomenon volume and neurological deterioration (OR 4.80, 95% CI 1.32-31.04, p  = 0.04) as well as poorer NIHSS score at hospital discharge (OR 3.73, 95% CI 1.52-10.78, p  = 0.007) was found. The discriminatory accuracy of steal phenomenon for neurological deterioration prediction had an AUC of 0.791 (95% CI 0.653-0.930)., Discussion: Based on our results we may distinguish two groups of patients with minor stroke currently ineligible for EVT, however, showing hemodynamic impairment and exhibiting neurological deterioration during hospitalization: (1) patients exhibiting steal phenomenon on BOLD-CVR imaging as well as hemodynamic impairment on resting perfusion imaging; (2) patients exhibiting steal phenomenon on BOLD-CVR imaging, however, no relevant hemodynamic impairment on resting perfusion imaging., Conclusion: The presence of BOLD-CVR derived steal phenomenon may aid to further study hemodynamic impairment in patients with minor LVO-AIS not eligible for EVT., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Abstract Background Bariatric surgery is an effective long-term weight loss strategy yielding improvements in neurocognitive function; however, the mechanism(s) responsible for these improvements remains unclear. Here, we assessed the feasibility of using magnetic resonance imaging (MRI) to evaluate whether cerebral vascular reactivity (CVR) is impaired in severely obese bariatric surgery candidates compared with normal weight healthy controls and whether CVR improves following bariatric surgery. We also investigated whether changes in CVR were associated with changes in cognitive function. Methods Bariatric surgery candidates (n = 6) were compared with normal weight healthy controls of a similar age (n = 10) at baseline, and then reassessed 2 weeks and 14 weeks following sleeve gastrectomy bariatric surgery. Young reference controls (n = 7) were also studied at baseline to establish the range of normal for each outcome measure. Microvascular and macrovascular CVR to hypercapnia (5% CO2) were assessed using blood-oxygen-level-dependent (BOLD) MRI, and changes in the middle cerebral artery (MCA) cross-sectional area, respectively. Cognitive function was assessed using a validated neurocognitive software. Results Compliance with the CVR protocol was high. Both macro- and micro-cerebrovascular function were highest in the young reference controls. Cognitive function was lower in obese bariatric surgery candidates compared with normal weight controls, and improved by 17% at 2 weeks and 21% by 14 weeks following bariatric surgery. To our surprise, whole-brain CVR BOLD did not differ between obese bariatric surgery candidates and normal weight controls of similar age (0.184 ± 0.101 vs. 0.192 ± 0.034 %BOLD/mmHgCO2), and did not change after bariatric surgery. In contrast, we observed vasoconstriction of the MCA during hypercapnia in 60% of the obese patients prior to surgery, which appeared to be abolished following bariatric surgery. Improvements in cognitive function were not associated with improvements in either CVR BOLD or MCA vasodilation after bariatric surgery. Conclusions Assessing CVR responses to a hypercapnic challenge with MRI was feasible in severely obese bariatric patients. However, no changes in whole-brain BOLD CVR were observed following bariatric surgery despite improvements in cognitive function. We recommend that future large trials assess CVR responses to cognitive tasks (rather than hypercapnia) to better define the mechanisms responsible for cognitive function improvements following bariatric surgery.

Background: Recent clinical studies suggest protective effects of SGLT2 inhibitors on kidney disease outcome. Chronic hypoxia has a critical role in kidney disease development, thus we speculated that canagliflozin, an SGLT2 inhibitor, can improve kidney oxygenation., Methods: A single-arm study was conducted to investigate the effects of canagliflozin on T2* value, which reflects oxygenation level, in patients with type 2 diabetes (T2D) using repeated blood oxygenation level-dependent MRI (BOLD MRI) examinations. Changes in cortical T2* from before (Day 0) to after single-dose treatment (Day 1) and after five consecutive treatments (Day 5) were evaluated using 12-layer concentric objects (TLCO) and region of interest (ROI) methods., Results: In the full analysis set (n=14 patients), the TLCO method showed no change of T2* with canagliflozin treatment, whereas the ROI method found that cortical T2* was significantly increased on Day 1 but not on Day 5. Sensitivity analysis using TLCO in 13 well-measured patients showed that canagliflozin significantly increased T2* on Day 1 with no change on Day 5, whereas a significant improvement in cortical T2* following canagliflozin treatment was found on both Day 1 and 5 using ROI., Conclusions: Short-term canagliflozin treatment may improve cortical oxygenation and lead to better kidney outcomes in patients with T2D., Competing Interests: KM has received speaker fees from Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co., Nippon Boehringer Ingelheim Co., Eli Lilly Japan K.K., AstraZeneca K.K., Ono Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Kyowa Kirin Co. Ltd., and Mochida Pharmaceutical Co. Ltd., and unrestricted research grants from Chugai Pharmaceutical Co. Ltd, Kyowa Kirin Co. Ltd., Torii Pharmaceutical Co. Ltd., and Sumitomo Pharma Co. Ltd., and research funding from Kyowa Kirin Co. Ltd. TI has received speaker fees from Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co., Nippon Boehringer Ingelheim Co., Eli Lilly Japan K.K., AstraZeneca K.K., Ono Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Kyowa Kirin Co. Ltd., Mochida Pharmaceutical Co. Ltd., Torii Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho CO., LTD., and Bayer Yakuhin, Ltd., and unrestricted research grant from Eli Lilly Japan K.K. HU has received speaker fees from Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co., Kyowa Kirin, and Mochida Pharmaceutical Co., Ltd. SN has received speaker fees from AstraZeneca K.K., Ono Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Novartis Pharmaceutical Co. Ltd., and Chugai Pharmaceutical Co. Ltd. ST has received speaker fees from Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Kyowa Kirin Co., Ltd., and Takeda Pharmaceutical Co., Ltd. HO has received speaker fees from Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co., Nippon Boehringer Ingelheim Co., Eli Lilly Japan K.K., AstraZeneca K.K., Ono Pharmaceutical Co. Ltd., Kyowa Kirin Co. Ltd., Novartis Pharmaceutical Co. Ltd., Torii Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd., and Bayer Pharmaceutical Co. Ltd., and unrestricted research grants from Ono Pharmaceutical Co. Ltd., Kyowa Kirin Co. Ltd., Torii Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., and Bayer Pharmaceutical Co. Ltd., and research funding from Kyowa Kirin Co. Ltd., Torii Pharmaceutical Co. Ltd., Kissei Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., and Bayer Pharmaceutical Co. Ltd. ME has received speaker fees from Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co., Sumitomo Pharma Co. Ltd., Sanofi K.K., Kyowa Kirin Co. Ltd., AstraZeneca K.K., and Ono Pharmaceutical Co. Ltd., and unrestricted research grants from Sumitomo Pharma Co. Ltd., Nippon Boehringer Ingelheim Co., Eisai Co. Ltd., Kyowa Kirin Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co. Ltd, and Bayer Pharmaceutical Co. Ltd. and research funding from Mitsubishi Tanabe Pharma Corporation and Kyowa Kirin Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mori, Inoue, Machiba, Uedono, Nakatani, Ishikawa, Taniuchi, Katayama, Yamamoto, Kobayashi, Kozawa, Shimono, Miki, Okada and Emoto.)

The brain relies on an effective clearance mechanism to remove metabolic waste products for the maintenance of homeostasis. Recent studies have focused on elucidating the forces that drive the motion of cerebrospinal fluid (CSF), responsible for removal of these waste products. We demonstrate that vascular responses evoked using controlled manipulations of partial pressure of carbon dioxide (PaCO 2 ) levels, serve as an endogenous driver of CSF clearance from the brain. To demonstrate this, we retrospectively surveyed our database, which consists of brain metastases patients from whom blood oxygen level-dependent (BOLD) images were acquired during targeted hypercapnic and hyperoxic respiratory challenges. We observed a correlation between CSF inflow signal around the fourth ventricle and CO 2 -induced changes in cerebral blood volume. By contrast, no inflow signal was observed in response to the nonvasoactive hyperoxic stimulus, validating our measurements. Moreover, our results establish a link between the rate of the hemodynamic response (to elevated PaCO 2 ) and peritumoral edema load, which we suspect may affect CSF flow, consequently having implications for brain clearance. Our expanded perspective on the factors involved in neurofluid flow underscores the importance of considering both cerebrovascular responses, as well as the brain mechanical properties, when evaluating CSF dynamics in the context of disease processes., (© 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Background and Purpose: Hemodynamic evaluation of moyamoya patients is crucial to decide the treatment strategy. Recently, CO2-triggered BOLD MRI has been shown to be a promising tool for the hemodynamic evaluation of moyamoya patients. However, the longitudinal reliability of this technique in follow-up examinations is unknown. This study aims to analyze longitudinal follow-up data of CO2-triggered BOLD MRI to prove the reliability of this technique for long-term control examinations in moyamoya patients. Methods: Longitudinal CO2 BOLD MRI follow-up examinations of moyamoya patients with and without surgical revascularization have been analyzed for all 6 vascular territories retrospectively. If revascularization was performed, any directly (by the disease or the bypass) or indirectly (due to change of collateral flow after revascularization) affected territory was excluded based on angiography findings (group 1). In patients without surgical revascularization between the MRI examinations, all territories were analyzed (group 2). Results: Eighteen moyamoya patients with 39 CO2 BOLD MRI examinations fulfilled the inclusion criteria. The median follow-up between the 2 examinations was 12 months (range 4–29 months). For 106 vascular territories analyzed in group 1, the intraclass correlation coefficient was 0.784, p < 0.001, and for group 2 (84 territories), it was 0.899, p < 0.001. Within the total follow-up duration of 140 patient months, none of the patients experienced a new stroke. Conclusions: CO2 BOLD MRI is a promising tool for mid- and long-term follow-up examinations of cerebral hemodynamics in moyamoya patients. Systematic prospective evaluation is required prior to making it a routine examination. [ABSTRACT FROM AUTHOR]

Background and Purpose: Dental implantation is thought to be associated with enhancement of neuro-cortical sensorimotor activity which has been lost due to an edentulous state. Such changes are either feeble or absent after the placement of a conventional denture. In the present study, we test this hypothesis using blood oxygen level-dependent (BOLD) activity on functional MRI (fMRI) as a bio-surrogate.Materials and Methods: fMRI was performed in 12 consecutive edentulous subjects (mean age = 59.2 years) after the placement of a conventional complete denture (CD) and subsequently after intraoral dental implantation (IOD). The semi-quantitative data of the BOLD activity was compiled to depict the activation seen in both scenarios in six anatomical regions. Statistical analysis was done to evaluate the significance of enhancement in BOLD activity in these regions in patients having an IOD as compared to those having a CD.Results: The enhancement of BOLD activity on fMRI after placement of an IOD was much more significant as compared to that noted with CD. Using Wilcoxon's signed-rank test the nonparametric data showed a significant positive elevation in global and regional assigned mean ranks of BOLD activity.Conclusion: Intraoral implantation leads to a significant elevation in the BOLD activity of the sensorimotor cortex as compared to the placement of a conventional CD. [ABSTRACT FROM AUTHOR]

Purpose: Examine the feasibility of characterizing the regulation of renal oxygenation using high‐temporal‐resolution monitoring of the T2∗ response to a step‐like oxygenation stimulus. Methods: For T2∗ mapping, multi‐echo gradient‐echo imaging was used (temporal resolution = 9 seconds). A step‐like renal oxygenation challenge was applied involving sequential exposure to hyperoxia (100% O2), hypoxia (10% O2 + 90% N2), and hyperoxia (100% O2). In vivo experiments were performed in healthy rats (N = 10) and in rats with bilateral ischemia‐reperfusion injury (N = 4). To assess the step response of renal oxygenation, a second‐order exponential model was used (model parameters: amplitude [A], time delay [Δt], damping constant [D], and period of the oscillation [T]) for renal cortex, outer stripe of the outer medulla, inner stripe of the outer medulla, and inner medulla. Results: The second‐order exponential model permitted us to model the exponential T2∗ recovery and the superimposed T2∗ oscillation following renal oxygenation stimulus. The in vivo experiments revealed a difference in Douter medulla between healthy controls (D < 1, indicating oscillatory recovery) and ischemia‐reperfusion injury (D > 1, reflecting aperiodic recovery). The increase in Douter medulla by a factor of 3.7 (outer stripe of the outer medulla) and 10.0 (inner stripe of the outer medulla) suggests that this parameter might be rather sensitive to (patho)physiological oxygenation changes. Conclusion: This study demonstrates the feasibility of monitoring the dynamic oxygenation response of renal tissues to a step‐like oxygenation challenge using high‐temporal‐resolution T2∗ mapping. Our results suggest that the implemented system analysis approach may help to unlock questions regarding regulation of renal oxygenation, with the ultimate goal of providing imaging means for diagnostics and therapy of renal diseases. [ABSTRACT FROM AUTHOR]

Crossed cerebellar diaschisis (CCD) in internal carotid artery (ICA) stroke refers to attenuated blood flow and energy metabolism in the contralateral cerebellar hemisphere. CCD is associated with an interruption of cerebro-cerebellar tracts, but the precise mechanism is unknown. We hypothesized that in patients with ICA occlusions, CCD might indicate severe hemodynamic impairment in addition to tissue damage. Duplex sonography and clinical data from stroke patients with unilateral ICAO who underwent blood oxygen-level-dependent MRI cerebrovascular reserve (BOLD-CVR) assessment were analysed. The presence of CCD (either CCD+ or CCD−) was inferred from BOLD-CVR. We considered regions with negative BOLD-CVR signal as areas suffering from hemodynamic steal. Twenty-five patients were included (11 CCD+ and 14 CCD−). Stroke deficits on admission and at 3 months were more severe in the CCD+ group. While infarct volumes were similar, CCD+ patients had markedly larger BOLD steal volumes than CCD− patients (median [IQR] 122.2 [111] vs. 11.6 [50.6] ml; p < 0.001). Furthermore, duplex revealed higher peak-systolic flow velocities in the intracranial collateral pathways. Strikingly, posterior cerebral artery (PCA)-P2 velocities strongly correlated with the National Institute of Health Stroke Scale on admission and BOLD-CVR steal volume. In patients with strokes due to ICAO, the presence of CCD indicated hemodynamic impairment with larger BOLD-defined steal volume and higher flow in the ACA/PCA collateral system. Our data support the concept of a vascular component of CCD as an indicator of hemodynamic failure in patients with ICAO. [ABSTRACT FROM AUTHOR]

Purpose: Venous cerebral blood volume (CBVv) is a major contributor to BOLD contrast, and therefore is an important parameter for understanding the underlying mechanism. Here, we propose a velocity‐selective venous spin labeling (VS‐VSL)‐prepared 3D turbo spin echo pulse sequence for whole‐brain baseline CBVv mapping. Methods: Unlike previous CBVv measurement techniques that exploit the interrelationship between BOLD signals and CBVv, in the proposed VS‐VSL technique both arterial blood and cerebrospinal fluid (CSF) signals were suppressed before the VS pulse train for exclusive labeling of venous blood, while a single‐slab 3D turbo spin echo readout was used because of its relative immunity to magnetic field variations. Furthermore, two approximations were made to the VS‐VSL signal model for simplified derivation of CBVv. In vivo studies were performed at 3T field strength in 8 healthy subjects. The performance of the proposed VS‐VSL method in baseline CBVv estimation was first evaluated in comparison to the existing, hyperoxia‐based method. Then, data were also acquired using VS‐VSL under hypercapnic and hyperoxic gas breathing challenges for further validation of the technique. Results: The proposed technique yielded physiologically plausible baseline CBVv values, and when compared with the hyperoxia‐based method, showed no statistical difference. Furthermore, data acquired using VS‐VSL yielded average CBVv of 2.89%/1.78%, 3.71%/2.29%, and 2.88%/1.76% for baseline, hypercapnia, and hyperoxia, respectively, in gray/white matter regions. As expected, hyperoxia had negligible effect (P >.8), whereas hypercapnia demonstrated vasodilation (P <<.01). Conclusion: Upon further validation of the quantification model, the method is expected to have merit for 3D CBVv measurements across the entire brain. [ABSTRACT FROM AUTHOR]

Introduction: Before using blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) during maternal hyperoxia as a method to detect individual placental dysfunction, it is necessary to understand spatiotemporal variations that represent normal placental function. We investigated the effect of maternal position and Braxton-Hicks contractions on estimates obtained from BOLD MRI of the placenta during maternal hyperoxia.Methods: For 24 uncomplicated singleton pregnancies (gestational age 27-36 weeks), two separate BOLD MRI datasets were acquired, one in the supine and one in the left lateral maternal position. The maternal oxygenation was adjusted as 5 min of room air (21% O2), followed by 5 min of 100% FiO2. After datasets were corrected for signal non-uniformities and motion, global and regional BOLD signal changes in R2* and voxel-wise Time-To-Plateau (TTP) in the placenta were measured. The overall placental and uterine volume changes were determined across time to detect contractions.Results: In mothers without contractions, increases in global placental R2* in the supine position were larger compared to the left lateral position with maternal hyperoxia. Maternal position did not alter global TTP but did result in regional changes in TTP. 57% of the subjects had Braxton-Hicks contractions and 58% of these had global placental R2* decreases during the contraction.Conclusion: Both maternal position and Braxton-Hicks contractions significantly affect global and regional changes in placental R2* and regional TTP. This suggests that both factors must be taken into account in analyses when comparing placental BOLD signals over time within and between individuals. [ABSTRACT FROM AUTHOR]

Purpose: There is ample evidence that systemic sympathetic neural activity contributes to the progression of chronic kidney disease, possibly by limiting renal blood flow and thereby inducing renal hypoxia. Up to now there have been no direct observations of this mechanism in humans. We studied the effects of systemic sympathetic activation elicited by a lower body negative pressure (LBNP) on renal blood flow (RBF) and renal oxygenation in healthy humans. Methods: Eight healthy volunteers (age 19–31 years) were subjected to progressive LBNP at − 15 and − 30 mmHg, 15 min per level. Brachial artery blood pressure was monitored intermittently. RBF was measured by phase-contrast MRI in the proximal renal artery. Renal vascular resistance was calculated as the MAP divided by the RBF. Renal oxygenation (R2*) was measured for the cortex and medulla by blood oxygen level dependent (BOLD) MRI, using a monoexponential fit. Results: With a LBNP of − 30 mmHg, pulse pressure decreased from 50 ± 10 to 43 ± 7 mmHg; MAP did not change. RBF decreased from 1152 ± 80 to 1038 ± 83 mL/min to 950 ± 67 mL/min at − 30 mmHg LBNP (p = 0.013). Heart rate and renal vascular resistance increased by 38 ± 15% and 23 ± 8% (p = 0.04) at − 30 mmHg LBNP, respectively. There was no change in cortical or medullary R2* (20.3 ± 1.2 s−1 vs 19.8 ± 0.43 s−1; 28.6 ± 1.1 s−1 vs 28.0 ± 1.3 s−1). Conclusion: The results suggest that an increase in sympathetic vasoconstrictor drive decreases kidney perfusion without a parallel reduction in oxygenation in healthy humans. This in turn indicates that sympathetic activation suppresses renal oxygen demand and supply equally, thus allowing adequate tissue oxygenation to be maintained. [ABSTRACT FROM AUTHOR]

The clinical significance of ipsilateral thalamic diaschisis (ITD) occurring after stroke is unknown. To characterize ITD, we investigate its hemodynamic, structural, and clinical implications. A single-institution prospective cross-sectional study was conducted using 28 symptomatic cerebrovascular steno-occlusive patients undergoing both BOLD-CVR and Diamox-challenged 15(O)-H2O-PET. Follow-up was at least three months. In addition, 15 age-matched healthy subjects were included. ITD was diagnosed based on a BOLD-CVR thalamic asymmetry index (TAI) > +2 standard deviations from healthy subjects. Cerebral blood flow differences were assessed using a PET-based TAI before and after Diamox challenge. Thalamic volume masks were determined using Freesurfer. Neurological status at symptom onset and after three months was determined with NIHSS and mRS scores. ITD was diagnosed in 15 of 28 (57%) patients. PET-TAI before and after Diamox challenge were increased in patients with ITD, indicating an ipsilateral thalamic blood flow decrease. Patients with ITD exhibited a marked ipsilateral thalamic volume decrease as compared to patients without ITD and healthy subjects. Furthermore, patients with ITD had worse NIHSS and mRS at symptom onset and after three months follow-up, even after adjustment for stroke volume. The presence of ITD is characterized by thalamic volume reduction, reduced thalamic blood flow, and worse neurological performance unrelated to stroke volume. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery is an effective long-term weight loss strategy yielding improvements in neurocognitive function; however, the mechanism(s) responsible for these improvements remains unclear. Here, we assessed the feasibility of using magnetic resonance imaging (MRI) to evaluate whether cerebral vascular reactivity (CVR) is impaired in severely obese bariatric surgery candidates compared with normal weight healthy controls and whether CVR improves following bariatric surgery. We also investigated whether changes in CVR were associated with changes in cognitive function. Methods: Bariatric surgery candidates (n = 6) were compared with normal weight healthy controls of a similar age (n = 10) at baseline, and then reassessed 2 weeks and 14 weeks following sleeve gastrectomy bariatric surgery. Young reference controls (n = 7) were also studied at baseline to establish the range of normal for each outcome measure. Microvascular and macrovascular CVR to hypercapnia (5% CO2) were assessed using blood-oxygen-level-dependent (BOLD) MRI, and changes in the middle cerebral artery (MCA) cross-sectional area, respectively. Cognitive function was assessed using a validated neurocognitive software. Results: Compliance with the CVR protocol was high. Both macro- and micro-cerebrovascular function were highest in the young reference controls. Cognitive function was lower in obese bariatric surgery candidates compared with normal weight controls, and improved by 17% at 2 weeks and 21% by 14 weeks following bariatric surgery. To our surprise, whole-brain CVR BOLD did not differ between obese bariatric surgery candidates and normal weight controls of similar age (0.184 ± 0.101 vs. 0.192 ± 0.034 %BOLD/mmHgCO2), and did not change after bariatric surgery. In contrast, we observed vasoconstriction of the MCA during hypercapnia in 60% of the obese patients prior to surgery, which appeared to be abolished following bariatric surgery. Improvements in cognitive function were not associated with improvements in either CVR BOLD or MCA vasodilation after bariatric surgery. Conclusions: Assessing CVR responses to a hypercapnic challenge with MRI was feasible in severely obese bariatric patients. However, no changes in whole-brain BOLD CVR were observed following bariatric surgery despite improvements in cognitive function. We recommend that future large trials assess CVR responses to cognitive tasks (rather than hypercapnia) to better define the mechanisms responsible for cognitive function improvements following bariatric surgery. [ABSTRACT FROM AUTHOR]

Blood oxygen level dependent (BOLD) MRI time series with maternal hyperoxia can assess placental oxygenation and function. Measuring precise BOLD changes in the placenta requires accurate temporal placental segmentation and is confounded by fetal and maternal motion, contractions, and hyperoxia-induced intensity changes. Current BOLD placenta segmentation methods warp a manually annotated subject-specific template to the entire time series. However, as the placenta is a thin, elongated, and highly non-rigid organ subject to large deformations and obfuscated edges, existing work cannot accurately segment the placental shape, especially near boundaries. In this work, we propose a machine learning segmentation framework for placental BOLD MRI and apply it to segmenting each volume in a time series. We use a placental-boundary weighted loss formulation and perform a comprehensive evaluation across several popular segmentation objectives. Our model is trained and tested on a cohort of 91 subjects containing healthy fetuses, fetuses with fetal growth restriction, and mothers with high BMI. Biomedically, our model performs reliably in segmenting volumes in both normoxic and hyperoxic points in the BOLD time series. We further find that boundary-weighting increases placental segmentation performance by 8.3% and 6.0% Dice coefficient for the cross-entropy and signed distance transform objectives, respectively., Competing Interests: Conflicts of Interest The authors declare no conflicts of interest.

Purpose: Literature reports contradicting results on the response of brain tumors to vascular stimuli measured in T2*-weighted MRI. Here, we analyzed the potential dependency of the MRI-response to (hypercapnic) hyperoxia on the order of the gas administration. Methods: T2* values were quantified at 3 Tesla in eight consenting patients at rest and during inhalation of hyperoxic/hypercapnic gas mixtures. Patients were randomly divided into two groups undergoing different gas administration protocols (group A: medical air-pure oxygen–carbogen; group B: medical air–carbogen-pure oxygen). Mann-Whitney U test and Wilcoxon signed rank test have been used to proof differences in T2* regarding respiratory challenge or different groups, respectively. Results: T2* values at rest for gray and white matter were 50.3 ± 2.6 ms and 46.1 ± 2.0 ms, respectively, and slightly increased during challenge. In tumor areas, T2* at rest were: necrosis = 74.1 ± 10.1 ms; edema = 60.3 ± 17.6 ms; contrast-enhancing lesions = 48.6 ± 20.7 ms; and solid T2-hyperintense lesions = 45.0 ± 3.0 ms. Contrast-enhancing lesions strongly responded to oxygen (+ 20.7%) regardless on the gas protocol (p = 0.482). However, the response to carbogen significantly depended on the order of gas administration (group A, + 18.6%; group B, − 6.4%, p = 0.042). In edemas, a different trend between group was found when breathing oxygen (group A, − 9.9%; group B, + 19.5%, p = 0.057). Conclusion: Preliminary results show a dependency of the T2* response of contrast-enhancing brain tumor lesions on the order of the gas administration. The gas administration protocol is an important factor in the interpretation of the T2*-response in areas of abnormal vascular growth. [ABSTRACT FROM AUTHOR]

Objectives: Cerebrovascular reactivity (CVR) measures the ability of cerebral blood vessels to change their diameter and, hence, their capacity to regulate regional blood flow in the brain. High resolution quantitative maps of CVR can be produced using blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in combination with a carbon dioxide stimulus, and these maps have become a useful tool in the clinical evaluation of cerebrovascular disorders. However, conventional CVR analysis does not fully characterize the BOLD response to a stimulus as certain regions of the brain are slower to react to the stimulus than others, especially in disease. Transfer function analysis (TFA) is an alternative technique that can account for dynamic temporal relations between signals and has recently been adapted for CVR computation. We investigated the application of TFA in data on children with sickle cell disease (SCD) and healthy controls, and compared them to results derived from conventional CVR analysis. Materials and methods: Data from 62 pediatric patients with SCD and 34 age-matched healthy controls were processed using conventional CVR analysis and TFA. BOLD data were acquired on a 3 Tesla MRI scanner while a carbon dioxide stimulus was quantified by sampling the end-tidal partial pressures of each exhaled breath. In addition, T1 weighted structural imaging was performed to identify grey and white matter regions for analysis. The TFA method generated maps representing both the relative magnitude change of the BOLD signal in response to the stimulus (Gain), as well as the BOLD signal speed of response (Phase) for each subject. These were compared to CVR maps calculated from conventional analysis. The effect of applying TFA on data from SCD patients versus controls was also examined. Results: The Gain measures derived from TFA were significantly higher than CVR values based on conventional analysis in both SCD patients and healthy controls, but the difference was greater in the SCD data. Moreover, while these differences were uniform across the grey and white matter regions of controls, they were greater in white matter than grey matter in the SCD group. Phase was also shown to be significantly correlated with the amount that TFA increases CVR estimates in both the grey and white matter. Conclusions: We demonstrated that conventional CVR analysis underestimates vessel reactivity and this effect is more prominent in patients with SCD. By using TFA, the resulting Gain and Phase measures more accurately characterize the BOLD response as it accounts for the temporal dynamics responsible for the CVR underestimation. We suggest that the additional information offered through TFA can provide insight into the mechanisms underlying CVR compromise in cerebrovascular diseases.

Determination of the humaneness of methods used to produce unconsciousness in animals, whether for anesthesia, euthanasia, humane slaughter, or depopulation, relies on our ability to assess stress, pain, and consciousness within the contexts of method and application. Determining the subjective experience of animals during transitional states of consciousness, however, can be quite difficult; further, loss of consciousness with different agents or methods may occur at substantially different rates. Stress and distress may manifest behaviorally (e.g., overt escape behaviors, approach-avoidance preferences [aversion]) or physiologically (e.g., movement, vocalization, changes in electroencephalographic activity, heart rate, sympathetic nervous system [SNS] activity, hypothalamic-pituitary axis [HPA] activity), such that a one-size-fits-all approach cannot be easily applied to evaluate methods or determine specific species applications. The purpose of this review is to discuss methods of evaluating stress in animals using physiologic methods, with emphasis on the transition between the conscious and unconscious states.

Purpose: The aim of this study was to evaluate the feasibility of renal oxygenation assessment using blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in the early period after kidney transplantation and to estimate its prognostic value for delayed graft function. Material and methods: Examinations were performed in 50 subjects: 40 patients within a week after the kidney transplantation and 10 healthy controls, using T2*-weighted sequence. Measurements in transplant patients were correlated to basic laboratory parameters in the early period after transplantation and at follow-up. Results: Examinations of seven patients (18%) were rejected due to their poor technical quality. Mean R2* values in transplant recipients were lower than in controls (11.6 vs. 15.9 Hz; p = 0.0001). An R2* value of 0.28 Hz was calculated as the minimal detectable change. There was no relation between R2* values and laboratory parameters. However, patients eGFR ≥ 40 ml/min/1.73 m2 presented higher R2* values than recipients eGFR < 40 ml/min/1.73 m2 (12.0 vs. 11.1 Hz; p = 0.0189). In ROC analysis R2* of ≤ 11.7 predicted an early reduced graft function with 0.82 sensitivity and 56% specificity (AUC = 0.708; p = 0.024) but was not useful for delayed graft function prediction (p > 0.7). Conclusions: Evaluation of renal graft oxygenation using BOLD MRI is technically challenging in the early period after transplantation. An R2* value of 0.28 Hz may in practice be considered as the minimal detectable change. The delayed graft function seems not to be dependent on early oxygenation values. Further, large-scale studies are necessary to confirm the latter observation. [ABSTRACT FROM AUTHOR]

Objective: Acute kidney injury (AKI) is an important risk factor for a number of adverse outcomes including end-stage renal disease and cardiovascular morbidity and mortality. Whilst many clinical situations that can induce AKI are known—e.g. drug toxicity, contrast agent exposure or ischemia during surgery—targeted preventive or therapeutic measures are still lacking. As to renoprotective strategies, remote ischemic preconditioning (RIPC) is one of the most promising novel approaches and has been examined by a number of clinical trials. The aim of this study was to use blood oxygenation level-dependent (BOLD) MRI as a surrogate parameter to assess the effect of RIPC in healthy volunteers.Materials and methods: In this IRB-approved, prospective study, 40 healthy volunteers were stratified with 20 undergoing an RIPC procedure (i.e. RIPC group) with a transient ischemia of the right arm, and 20 undergoing a sham procedure. Before and after the procedure, both kidneys of all participants were scanned using a 12-echo mGRE sequence for functional BOLD imaging at 3T. For each volunteer, 180 ROIs were placed in the cortex and the medulla of the kidneys. Ultimately, R2* values, which have an inverse correlation with the oxygenation level of tissue, were averaged for the RIPC and control groups.Results: Following intervention, mean R2* values significantly decreased in the RIPC group in both the cortex (18.6 ± 2.3 vs. 17.5 ± 1.7 Hz; p = 0.0047) and medulla (34 ± 5.2 vs. 32.2 ± 4.2 Hz; p = 0.0001). However, no significant differences were observed in the control group.Conclusion: RIPC can be non-invasively assessed in healthy volunteers using BOLD MRI at 3T, demonstrating a higher oxygen content in kidney tissue. This study presents a first-in-man trial establishing a quantifiable readout of RIPC and its effects on kidney physiology. BOLD measurements may advance clinical trials in further evaluating RIPC for future clinical care. [ABSTRACT FROM AUTHOR]

Objectives: Human pregnancies complicated by placental dysfunction may be characterized by a high hyperoxic Blood oxygen level-dependent (BOLD) MRI response. The pathophysiology behind this phenomenon remains to be established. The aim of this study was to evaluate whether it is associated with altered placental baseline conditions, including a lower oxygenation and altered tissue morphology, as estimated by the placental transverse relaxation time (T2*).Method: We included 49 normal pregnancies (controls) and 13 pregnancies complicated by placental dysfunction (cases), defined by a birth weight < 10th percentile in combination with placental pathological signs of vascular malperfusion. During maternal oxygen inhalation, we measured the relative ΔBOLD response ((hyperoxic BOLD - baseline BOLD)/baseline BOLD) from a dynamic single-echo gradient-recalled echo (GRE) MRI sequence and the absolute ΔT2* (hyperoxic T2*- baseline T2*) from breath-hold multi-echo GRE sequences.Results: In the control group, the relative ΔBOLD response increased during gestation from 5% in gestational week 20 to 20% in week 40. In the case group, the relative ΔBOLD response was significantly higher (mean Z-score 4.94; 95% CI 2.41, 7.47). The absolute ΔT2*, however, did not differ between controls and cases (p = 0.37), whereas the baseline T2* was lower among cases (mean Z-score -3.13; 95% CI -3.94, -2.32). Furthermore, we demonstrated a strong negative linear correlation between the Log10 ΔBOLD response and the baseline T2* (r = -0.88, p < 0.0001).Conclusion: The high hyperoxic ΔBOLD response demonstrated in pregnancies complicated by placental dysfunction may simply reflect altered baseline conditions, as the absolute increase in placental oxygenation (ΔT2*) does not differ between groups. [ABSTRACT FROM AUTHOR]

Kidney volume is regarded as the most precise indicator of kidney size. However, volume assessment is not widely used clinically because its measurement is difficult due to the complex kidney shape. Apart from the conventional methods of measurement of renal dimensions from X-rays, ultrasound scan, computed tomography scan and magnetic resonance imaging have evolved as the three best modalities for this purpose currently. Assessment of kidney size should also be made individually since many factors like body mass index, height, gender, age, position of kidneys, sex, stenoses and number of renal arteries influence the measurements. In this paper, we have critically analysed the advantages and disadvantages of the various methods of renal morphometry, by reviewing the literature spanning over the period of 1976 - 2009.

Purpose To characterize spatial patterns of [ABSTRACT FROM AUTHOR]

Purpose: To evaluate blood oxygenation level-dependent (BOLD) contrast changes in healthy breast parenchyma and breast carcinoma during administration of vasoactive gas stimuli.Materials and Methods: Magnetic resonance imaging (MRI) was performed at 3T in 19 healthy premenopausal female volunteers using a single-shot fast spin echo sequence to acquire dynamic T2 -weighted images. 2% (n = 9) and 5% (n = 10) carbogen gas mixtures were interleaved with either medical air or oxygen in 2-minute blocks, for four complete cycles. A 12-minute medical air breathing period was used to determine background physiological modulation. Pixel-wise correlation analysis was applied to evaluate response to the stimuli in breast parenchyma and these results were compared to the all-air control. The relative BOLD effect size was compared between two groups of volunteers scanned in different phases of the menstrual cycle. The optimal stimulus design was evaluated in five breast cancer patients.Results: Of the four stimulus combinations tested, oxygen vs. 5% carbogen produced a response that was significantly stronger (P < 0.05) than air-only breathing in volunteers. Subjects imaged during the follicular phase of their cycle when estrogen levels typically peak exhibited a significantly smaller BOLD response (P = 0.01). Results in malignant tissue were variable, with three out of five lesions exhibiting a diminished response to the gas stimulus.Conclusion: Oxygen vs. 5% carbogen is the most robust stimulus for inducing BOLD contrast, consistent with the opposing vasomotor effects of these two gases. Measurements may be confounded by background physiological fluctuations and menstrual cycle changes. J. Magn. Reson. Imaging 2016;44:335-345. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the reproducibility of cerebrovascular reactivity (CVR) measurements acquired in children using magnetic resonance imaging (MRI) in combination with a computer-controlled carbon dioxide (CO2 ) stimulus. Materials and Methods: Ten healthy children (age 16.1 ± 1.6 years) underwent CVR imaging on a 3T scanner using a blood-oxygen level-dependent (BOLD) MRI sequence. Targeted hypercapnia was induced during imaging with a CO2 gas challenge delivered using a specialized gas sequencer (RespirAct). A total of four BOLD scans were performed over 2 separate days to test within-day and between-day consistency of the data. CVR values were computed by correlating the relative change in BOLD signal in response to the CO2 stimulus delivered to the each subject. Results: Intraclass correlation coefficients (ICCs) of within-day values show highly reproducible measures in both the gray matter (ICC = 0.857, P < 0.001) and white matter (ICC = 0.895, P < 0.001). Relatively lower between-day reproducibility was observed in both the gray matter (ICC = 0.776, P = 0.001) and white matter (ICC = 0.719, P = 0.004). Conclusion: Using a computer-controlled CO2 stimulus, we have demonstrated the reliability of BOLD-CVR measurements in pediatric subjects. Within-day and between-day metrics of reproducibility were comparable to adult data. [ABSTRACT FROM AUTHOR]

Objectives: During placental Blood Oxygen Level Dependent (BOLD) Magnetic Resonance Imaging (MRI), we have observed spontaneous reductions in placental oxygenation lasting 2-4 min. We hypothesize, that these reductions in placental oxygenation are caused by subclinical uterine contractions. Methods: We evaluated placental oxygenation during a five-minute placental BOLD MRI in 56 normal pregnancies (gestational week 23-40) and observed a spontaneous reduction in eight cases. The 56 BOLD MRIs were systematically analyzed for signs of uterine contractions, i.e. visual changes in uterus shape and reductions in the number of pixels within Regions of interest (ROI) covering the outline of the entire uterus. Results: The eight reductions in the BOLD signal lasted for 217 ± 51 (mean ± SD) seconds with an average signal loss of 17 ± 5%. They were all associated with a contraction, which started 43 ± 21 s prior to the start of the reduction and ended 71 ± 30 s prior to the end of the reduction. In the remaining 48 MRIs, we observed no contraction. Conclusion: We suggest that the observed spontaneous reductions in placental oxygenation are caused by uterine contractions. According to our data, subclinical uterine contractions occur regularly and have a markedly impact on placental oxygenation. Therefore, uterine contractions need to be considered in the interpretation of placental MRI as they may interfere with the MRI results. [ABSTRACT FROM AUTHOR]

Determination of the humaneness of methods used to produce unconsciousness in animals, whether for anesthesia, euthanasia, humane slaughter, or depopulation, relies on our ability to assess stress, pain, and consciousness within the contexts of method and application. Determining the subjective experience of animals during transitional states of consciousness, however, can be quite difficult; further, loss of consciousness with different agents or methods may occur at substantially different rates. Stress and distress may manifest behaviorally (e.g., overt escape behaviors, approach-avoidance preferences [aversion]) or physiologically (e.g., movement, vocalization, changes in electroencephalographic activity, heart rate, sympathetic nervous system [SNS] activity, hypothalamic-pituitary axis [HPA] activity), such that a one-size-fits-all approach cannot be easily applied to evaluate methods or determine specific species applications. The purpose of this review is to discuss methods of evaluating stress in animals using physiologic methods, with emphasis on the transition between the conscious and unconscious states. [ABSTRACT FROM AUTHOR]

Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) has recently emerged as an important noninvasive technique to assess intrarenal oxygenation under physiologic and pathophysiologic conditions. Although this tool represents a major addition to our armamentarium of methodologies to investigate the role of hypoxia in the pathogenesis of acute kidney injury and progressive chronic kidney disease, numerous technical limitations confound interpretation of data derived from this approach. BOLD MRI has been utilized to assess intrarenal oxygenation in numerous experimental models of kidney disease and in human subjects with diabetic and nondiabetic chronic kidney disease, acute kidney injury, renal allograft rejection, contrast-associated nephropathy, and obstructive uropathy. However, confidence in conclusions based on data derived from BOLD MRI measurements will require continuing advances and technical refinements in the use of this technique. [ABSTRACT FROM AUTHOR]

Background and purpose: Intravascular angioplasty and stenting of intracranial arterial stenosis provided controversial results. Besides the expertise of the practitioners, the selection of the patients remains challenging. BOLD MRI of the cerebral vasoreactivity (BOLD MRI CVR) to hypercapnia provides reproducible maps of the entire brain of the vascular reserve, and could be helpful to assess the best therapeutic strategy. Case history: We report the case of a 63-year-old woman referred for a severe stenosis of the proximal portion of the left middle cerebral artery, revealed by a lenticulostriate and precentral infarction. Despite an aggressive medical treatment during 5 months, the occurrence of iterative transient ischemic attacks motivated intravascular stenting. Functional MRI of the vasoreactivity to hypercapnia using both Blood Oxygen Level Dependent (BOLD) and arterial spin labeling sequences showed normal basal perfusion and impaired vasoreactivity in the left middle cerebral artery territory. Three months after stenting, the BOLD MRI CVR showed vasoreactivity normalization. Since, the patient remains free of ischemic disorders one year after stenting. Conclusion: BOLD MRI of the CVR to hypercapnia may be helpful to optimize the treatment of patients with intracranial arterial stenosis, and could be performed in future therapeutic trials. Hum Brain Mapp 35:1320-1324, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]