Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI.
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ABSTRACT: Purpose
Gadolinium-based dynamic susceptibility contrast (DSC) is commonly used to characterize blood flow in patients with stroke and brain tumors. Unfortunately, gadolinium contrast administration has been associated with adverse reactions and long-term accumulation in tissues. In this work, we propose an alternative deoxygenation-based DSC (dDSC) method that uses a transient hypoxia gas paradigm to deliver a bolus of paramagnetic deoxygenated hemoglobin to the cerebral vasculature for perfusion imaging.Methods
Through traditional DSC tracer kinetic modeling, the MR signal change induced by this hypoxic bolus can be used to generate regional perfusion maps of cerebral blood flow, cerebral blood volume, and mean transit time. This gas paradigm and blood-oxygen-level-dependent (BOLD)-MRI were performed concurrently on a cohort of 66 healthy and chronically anemic subjects (age 23.5 ± 9.7, female 64%).Results
Our results showed reasonable global and regional agreement between dDSC and other flow techniques, such as phase contrast and arterial spin labeling.Conclusion
In this proof-of-concept study, we demonstrated the feasibility of using transient hypoxia to generate a contrast bolus that mimics the effect of gadolinium and yields reasonable perfusion estimates. Looking forward, optimization of the hypoxia boluses and measurement of the arterial-input function is necessary to improve the accuracy of dDSC. Additionally, a cross-validation study of dDSC and DSC in brain tumor and ischemic stroke subjects is warranted to evaluate the clinical diagnostic utility of this approach.
SUBMITTER: Vu C
PROVIDER: S-EPMC7728454 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundObstructive sleep apnea and nocturnal oxygen desaturations, which are prevalent in sickle cell disease (SCD) and chronic anemia disorders, have been linked to risks of stroke and silent cerebral infarcts (SCI). Cerebrovascular response to intermittent desaturations has not been well studied and may identify patients at greatest risk.PurposeTo investigate the cerebral dynamic response to induced desaturation in SCD patients with and without SCI, chronic anemia, and healthy subjects.Study typeProspective.SubjectsTwenty-six SCD patients (age = 21 ± 8.2, female 46.2%), including 15 subjects without SCI and nine subjects with SCI, 15 nonsickle anemic patients (age = 22 ± 5.8, female 66.7%), and 31 controls (age = 28 ± 12.3, female 77.4%).Field strength/sequence3T, gradient-echo echo-planar imaging.AssessmentA transient hypoxia challenge of five breaths of 100% nitrogen gas was performed with blood oxygen level-dependent (BOLD) MRI and near-infrared spectroscopy (NIRS) acquisitions. Hypoxia responses were characterized by desaturation depth, time-to-peak, return-to-baseline half-life, and posthypoxia recovery in the BOLD and NIRS time courses. SCI were documented by T2 fluid-attenuation inversion recovery (FLAIR).Statistical testsUnivariate and multivariate regressions were performed between hypoxic parameters and anemia predictors. Voxelwise two-sample t-statistic maps were used to assess the regional difference in hypoxic responses between anemic and control groups.ResultsCompared to controls, SCD and chronically anemic patients demonstrated significantly higher desaturation depth (P < 0.01) and shorter return-to-baseline timing response (P < 0.01). Patients having SCI had shorter time-to-peak (P < 0.01), return-to-baseline (P < 0.01), and larger desaturation depth (P < 0.01) in both white matter regions at risk and normal-appearing white matter than patients without infarcts. On multivariate analysis, desaturation depth and timing varied with age, sex, blood flow, white blood cells, and cell-free hemoglobin (r2 = 0.25 for desaturation depth; r2 = 0.18 for time-to-peak; r2 = 0.37 for return-to-baseline).Data conclusionTransient hypoxia revealed global and regional response differences between anemic and healthy subjects. SCI was associated with extensive heterogeneity of desaturation dynamics, consistent with extensive underlying microvascular remodeling.
| S-EPMC7655661 | biostudies-literature
Project description:Magnetic resonance imaging (MRI)-based quantification of the blood-oxygenation-level-dependent (BOLD) effect allows oxygen extraction fraction (OEF) mapping. The multi-parametric quantitative BOLD (mq-BOLD) technique facilitates relative OEF (rOEF) measurements with whole brain coverage in clinically applicable scan times. Mq-BOLD requires three separate scans of cerebral blood volume and transverse relaxation rates measured by gradient-echo (1/T2∗) and spin-echo (1/T2). Although the current method is of clinical merit in patients with stroke, glioma and internal carotid artery stenosis (ICAS), there are relaxation measurement artefacts that impede the sensitivity of mq-BOLD and artificially elevate reported rOEF values. We posited that T2-related biases caused by slice refocusing imperfections during rapid 2D-GraSE (Gradient and Spin Echo) imaging can be reduced by applying 3D-GraSE imaging sequences, because the latter requires no slice selective pulses. The removal of T2-related biases would decrease overestimated rOEF values measured by mq-BOLD. We characterized effects of T2-related bias in mq-BOLD by comparing the initially employed 2D-GraSE and two proposed 3D-GraSE sequences to multiple single spin-echo reference measurements, both in vitro and in vivo. A phantom and 25 participants, including young and elderly healthy controls as well as ICAS-patients, were scanned. We additionally proposed a procedure to reliably identify and exclude artefact affected voxels. In the phantom, 3D-GraSE derived T2 values had 57% lower deviation from the reference. For in vivo scans, the formerly overestimated rOEF was reduced by -27% (p < 0.001). We obtained rOEF = 0.51, which is much closer to literature values from positron emission tomography (PET) measurements. Furthermore, increased sensitivity to a focal rOEF elevation in an ICAS-patient was demonstrated. In summary, the application of 3D-GraSE improves the mq-BOLD-based rOEF quantification while maintaining clinically feasible scan times. Thus, mq-BOLD with non-slice selective T2 imaging is highly promising to improve clinical diagnostics of cerebrovascular diseases such as ICAS.
| S-EPMC7730517 | biostudies-literature
Project description:BackgroundMyocardial perfusion reflects the macro- and microvascular coronary circulation. Recent quantitation developments using cardiovascular magnetic resonance perfusion permit automated measurement clinically. We explored the prognostic significance of stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR, the ratio of stress to rest MBF).MethodsA 2-center study of patients with both suspected and known coronary artery disease referred clinically for perfusion assessment. Image analysis was performed automatically using a novel artificial intelligence approach deriving global and regional stress and rest MBF and MPR. Cox proportional hazard models adjusting for comorbidities and cardiovascular magnetic resonance parameters sought associations of stress MBF and MPR with death and major adverse cardiovascular events (MACE), including myocardial infarction, stroke, heart failure hospitalization, late (>90 day) revascularization, and death.ResultsA total of 1049 patients were included with a median follow-up of 605 (interquartile range, 464-814) days. There were 42 (4.0%) deaths and 188 MACE in 174 (16.6%) patients. Stress MBF and MPR were independently associated with both death and MACE. For each 1 mL·g-1·min-1 decrease in stress MBF, the adjusted hazard ratios for death and MACE were 1.93 (95% CI, 1.08-3.48, P=0.028) and 2.14 (95% CI, 1.58-2.90, P<0.0001), respectively, even after adjusting for age and comorbidity. For each 1 U decrease in MPR, the adjusted hazard ratios for death and MACE were 2.45 (95% CI, 1.42-4.24, P=0.001) and 1.74 (95% CI, 1.36-2.22, P<0.0001), respectively. In patients without regional perfusion defects on clinical read and no known macrovascular coronary artery disease (n=783), MPR remained independently associated with death and MACE, with stress MBF remaining associated with MACE only.ConclusionsIn patients with known or suspected coronary artery disease, reduced MBF and MPR measured automatically inline using artificial intelligence quantification of cardiovascular magnetic resonance perfusion mapping provides a strong, independent predictor of adverse cardiovascular outcomes.
| S-EPMC7176346 | biostudies-literature
Project description:Previous work has shown that combining dynamic contrast-enhanced (DCE)-MRI and oxygen-enhanced (OE)-MRI binary enhancement maps can identify tumor hypoxia. The current work proposes a novel, data-driven method for mapping tissue oxygenation and perfusion heterogeneity, based on clustering DCE/OE-MRI data.DCE-MRI and OE-MRI were performed on nine U87 (glioblastoma) and seven Calu6 (non-small cell lung cancer) murine xenograft tumors. Area under the curve and principal component analysis features were calculated and clustered separately using Gaussian mixture modelling. Evaluation metrics were calculated to determine the optimum feature set and cluster number. Outputs were quantitatively compared with a previous non data-driven approach.The optimum method located six robustly identifiable clusters in the data, yielding tumor region maps with spatially contiguous regions in a rim-core structure, suggesting a biological basis. Mean within-cluster enhancement curves showed physiologically distinct, intuitive kinetics of enhancement. Regions of DCE/OE-MRI enhancement mismatch were located, and voxel categorization agreed well with the previous non data-driven approach (Cohen's kappa?=?0.61, proportional agreement?=?0.75).The proposed method locates similar regions to the previous published method of binarization of DCE/OE-MRI enhancement, but renders a finer segmentation of intra-tumoral oxygenation and perfusion. This could aid in understanding the tumor microenvironment and its heterogeneity. Magn Reson Med 79:2236-2245, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
| S-EPMC5836865 | biostudies-other
Project description:In conventional neuroimaging, cerebrovascular reactivity (CVR) is quantified primarily using the blood-oxygenation level-dependent (BOLD) functional MRI (fMRI) signal, specifically, as the BOLD response to intravascular carbon dioxide (CO2) modulations, in units of [%?BOLD/mmHg]. While this method has achieved wide appeal and clinical translation, the tolerability of CO2-related tasks amongst patients and the elderly remains a challenge in more routine and large-scale applications. In this work, we propose an improved method to quantify CVR by exploiting intrinsic fluctuations in CO2 and corresponding changes in the resting-state BOLD signal (rs-qCVR). Our rs-qCVR approach requires simultaneous monitoring of PETCO2, cardiac pulsation and respiratory volume. In 16 healthy adults, we compare our quantitative CVR estimation technique to the prospective CO2-targeting based CVR quantification approach (qCVR, the "standard"). We also compare our rs-CVR to non-quantitative alternatives including the resting-state fluctuation amplitude (RSFA), amplitude of low-frequency fluctuation (ALFF) and global-signal regression. When all subjects were pooled, only RSFA and ALFF were significantly associated with qCVR. However, for characterizing regional CVR variations within each subject, only the PETCO2-based rs-qCVR measure is strongly associated with standard qCVR in 100% of the subjects (p?0.1). In contrast, for the more qualitative CVR measures, significant within-subject association with qCVR was only achieved in 50-70% of the subjects. Our work establishes the feasibility of extracting quantitative CVR maps using rs-fMRI, opening the possibility of mapping functional connectivity and qCVR simultaneously.
| S-EPMC5148619 | biostudies-literature
Project description:BACKGROUND:Quantitative myocardial perfusion cardiac MRI can provide a fast and robust assessment of myocardial perfusion status for the noninvasive diagnosis of myocardial ischemia while being more objective than visual assessment. However, it currently has limited use in clinical practice due to the challenging postprocessing required, particularly the segmentation. PURPOSE:To evaluate the efficacy of an automated deep learning (DL) pipeline for image processing prior to quantitative analysis. STUDY TYPE:Retrospective. POPULATION:In all, 175 (350 MRI scans; 1050 image series) clinical patients under both rest and stress conditions (135/10/30 training/validation/test). FIELD STRENGTH/SEQUENCE:3.0T/2D multislice saturation recovery T1 -weighted gradient echo sequence. ASSESSMENT:Accuracy was assessed, as compared to the manual operator, through the mean square error of the distance between landmarks and the Dice similarity coefficient of the segmentation and bounding box detection. Quantitative perfusion maps obtained using the automated DL-based processing were compared to the results obtained with the manually processed images. STATISTICAL TESTS:Bland-Altman plots and intraclass correlation coefficient (ICC) were used to assess the myocardial blood flow (MBF) obtained using the automated DL pipeline, as compared to values obtained by a manual operator. RESULTS:The mean (SD) error in the detection of the time of peak signal enhancement in the left ventricle was 1.49 (1.4) timeframes. The mean (SD) Dice similarity coefficients for the bounding box and myocardial segmentation were 0.93 (0.03) and 0.80 (0.06), respectively. The mean (SD) error in the RV insertion point was 2.8 (1.8) mm. The Bland-Altman plots showed a bias of 2.6% of the mean MBF between the automated and manually processed MBF values on a per-myocardial segment basis. The ICC was 0.89, 95% confidence interval = [0.87, 0.90]. DATA CONCLUSION:We showed high accuracy, compared to manual processing, for the DL-based processing of myocardial perfusion data leading to quantitative values that are similar to those achieved with manual processing. LEVEL OF EVIDENCE:3 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1689-1696.
| S-EPMC7317373 | biostudies-literature
Project description:To evaluate the interstudy repeatability of multislice quantitative cardiovascular magnetic resonance myocardial blood flow (MBF), myocardial perfusion reserve (MPR), and extracellular volume (ECV). A unique saturation recovery self-gated acquisition was used for the perfusion scans.An ungated golden angle radial turboFLASH pulse sequence was used to scan 10 subjects on two separate days on a 3T scanner. A single saturation pulse was followed by a set of four slices. Rest and hyperemia scans were acquired during free breathing. The images were reconstructed using an iterative algorithm with spatiotemporal constraints. The ungated images were retrospectively binned (self-gated) into near-systole and near-diastole. Deformable registration was performed to adjust for respiratory and residual cardiac motion, and the data were fit with a Fermi model to estimate the interstudy repeatability of quantitative self-gated MBF and MPR.The coefficient of variation (CoV) of the territorial MPR using the self-gated near-systole data was 18.6%. The self-gated near-diastole data gave less good CoV of MPR, equal to 46.2%. For MBFs, and using smaller (segmental) regions, the CoVs were 20.1% and 22.7% for the estimation of myocardial blood flow at stress and rest, respectively, using the self-gated near-systole data. The self-gated near-diastole data gave CoV?=?48.6% and 44.9% for stress and rest.The self-gated free-breathing technique for quantification of myocardial blood flow showed good repeatability for near-systole, with results comparable to published studies on interstudy repeatability of quantitative myocardial perfusion MRI using ECG-gating and breath-holds. Self-gated near-diastole data results were less repeatable. J. Magn. Reson. Imaging 2016;43:1369-1378.
| S-EPMC4865416 | biostudies-other
Project description:PURPOSE:The aim of this study was to develop a portable perfusion phantom and validate its utility in quantitative dynamic contrast-enhanced magnetic resonance imaging of the abdomen. METHODS:A portable perfusion phantom yielding a reproducible contrast enhancement curve (CEC) was developed. A phantom package including perfusion and static phantoms were imaged simultaneously with each of three healthy human volunteers in two different 3T MR scanners. Look-up tables correlating reference (known) contrast concentrations with measured ones were created using either the static or perfusion phantom. Contrast maps of image slices showing four organs (liver, spleen, pancreas, and paravertebral muscle) were generated before and after data correction using the look-up tables. The contrast concentrations at 4.5 min after dosing in each of the four organs were averaged for each volunteer. The mean contrast concentrations (4 organs × 3 volunteers = 12) were compared for the two scanners, and the intra-class correlation coefficient (ICC) was calculated. Also, the ICC of the mean Ktrans values between the two scanners was calculated before and after data correction. RESULTS:The repeatability coefficient of CECs of perfusion phantom was higher than 0.997 in all measurements. The ICC of the tissue contrast concentrations between the two scanners was 0.693 before correction, but increased to 0.974 after correction using the look-up tables (LUTs) of perfusion phantom. However, the ICC was not increased after correction using static phantom (ICC: 0.617). Similarly, the ICC of the Ktrans values was 0.899 before correction, but increased to 0.996 after correction using perfusion phantom LUTs. The ICC of the Ktrans values, however, was not increased when static phantom LUTs were used (ICC: 0.866). CONCLUSIONS:The perfusion phantom reduced variability in quantitating contrast concentration and Ktrans values of human abdominal tissues across different MR units, but static phantom did not. The perfusion phantom has the potential to facilitate multi-institutional clinical trials employing quantitative DCE-MRI to evaluate various abdominal malignancies.
| S-EPMC5646228 | biostudies-literature
Project description:ObjectivesDeconvolution-derived maps of CT perfusion (CTP) data may be confounded by transit delays. We propose temporal similarity perfusion (TSP) analysis to decrease CTP maps' dependence on transit times and investigate its sensitivity to detect perfusion deficits.MethodsCTP data of acute stroke patients obtained within 9 h of symptom onset was analyzed using a delay-insensitive singular value decomposition method and with TSP. The TSP method applies an iterative process whereby a pixel's highest Pearson's R value is obtained through comparison of a pixel's time-shifted signal density time-series curve and the average whole brain signal density time-series curve. Our evaluation included a qualitative and quantitative rating of deconvolution maps (MTT, CBV, and TTP), of TSP maps, and of follow-up CT.ResultsSixty-five patients (mean 68 (SD 13) years, 34 male) were included. A perfusion deficit was identified in 90%, 86%, 65%, and 84% of MTT, TTP, CBV, and TSP maps. The agreement of MTT, TTP, and TSP with CT follow-up was comparable but noticeably lower for CBV. CBV had the best relationship with final infarct volume (R2 = 0.77, p < 0.001), followed by TSP (R2 = 0.63, p < 0.001). Intra-rater agreement of an inexperienced reader was higher for TSP than for CBV/MTT maps (kappa's of 0.79-0.84 and 0.63-0.7). Inter-rater agreement for experienced readers was comparable across maps.ConclusionsTSP maps are easier to interpret for inexperienced readers. Perfusion deficits detected by TSP are smaller which may suggest less dependence on transit delays although more investigation is required.Key points• Temporal similarity perfusion mapping assesses CTP data based on similarities in signal time-curves. • TSP maps are comparable in perfusion deficit detection to deconvolution maps. • TSP maps are easier to interpret for inexperienced readers.
| S-EPMC7295083 | biostudies-literature
Project description:PurposeTo present a novel MR pulse sequence and modeling algorithm to quantify the water exchange rate (kw ) across the blood-brain barrier (BBB) without contrast, and to evaluate its clinical utility in a cohort of elderly subjects at risk of cerebral small vessel disease (SVD).MethodsA diffusion preparation module with spoiling of non-Carr-Purcell-Meiboom-Gill signals was integrated with pseudo-continuous arterial spin labeling (pCASL) and 3D gradient and spin echo (GRASE) readout. The tissue/capillary fraction of the arterial spin labeling (ASL) signal was separated by appropriate diffusion weighting (b = 50 s/mm2 ). kw was quantified using a single-pass approximation (SPA) model with total generalized variation (TGV) regularization. Nineteen elderly subjects were recruited and underwent 2 MRIs to evaluate the reproducibility of the proposed technique. Correlation analysis was performed between kw and vascular risk factors, Clinical Dementia Rating (CDR) scale, neurocognitive assessments, and white matter hyperintensity (WMH).ResultsThe capillary/tissue fraction of ASL signal can be reliably differentiated with the diffusion weighting of b = 50 s/mm2 , given ~100-fold difference between the (pseudo-)diffusion coefficients of the 2 compartments. Good reproducibility of kw measurements (intraclass correlation coefficient = 0.75) was achieved. Average kw was 105.0 ± 20.6, 109.6 ± 18.9, and 94.1 ± 19.6 min-1 for whole brain, gray and white matter. kw was increased by 28.2%/19.5% in subjects with diabetes/hypercholesterolemia. Significant correlations between kw and vascular risk factors, CDR, executive/memory function, and the Fazekas scale of WMH were observed.ConclusionA diffusion prepared 3D GRASE pCASL sequence with TGV regularized SPA modeling was proposed to measure BBB water permeability noninvasively with good reproducibility. kw may serve as an imaging marker of cerebral SVD and associated cognitive impairment.
| S-EPMC6414249 | biostudies-literature