Transient susceptibility imaging as a measure of hemodynamic compromise: A pilot study.

BACKGROUND AND PURPOSE: The purpose of this study was to test the hypothesis that hemodynamically compromised brains exhibit transient changes in magnetic susceptibility throughout the cardiac cycle, and to model these changes using Linear System Theory to extract an index that reflects cerebrovascular reserve. MATERIALS AND METHODS: Eleven patients with angiographically-confirmed intracranial atherosclerotic disease with >50% stenosis were imaged with susceptibility weighted, cardiac-gated single shot images of cerebral Oxygen Extraction Fraction (OEF) at different timepoints of the cardiac cycle. Cardiac gating of the OEF acquisition allowed interrogation of oxygenated blood and the detection of changes throughout the cardiac cycle. Independent component analysis (ICA) of raw k-space data across the cardiac phase allowed MRI signal decomposition into dynamic and static components for image reconstruction. An asymmetry index score of the resultant parametric images were compared to test the hypothesis that variation in hemoglobin-induced susceptibility across the cardiac cycle indeed reflects pathophysiology of cerebrovascular disease. A mathematical model was derived to parameterize physiologic changes induced by the presence of a hemodynamically significant stenosis in the brain as a tissue impulse response parameter (ß). RESULTS: OEF was elevated in the affected hemisphere (50.34 ± 12.13% vs 46.93 ± 12.34%), but failed to reach statistical significance (p < .0796). Transient changes in the OEF signal showed significant distinction between healthy and compromised tissue (0.56 ± 0.067 vs 0.44 ± 0.067, p < .019)). The derived tissue impulse response function was found to be significant as well (10.72 ± 3.48 10-3 ms-1, 9.69 ± 3.51 10-3 ms-1; p < .037). CONCLUSION: In this pilot study, we found transient OEF and ß to be significant predictors of hemispheric compromise.

Predictive Value of Coronary Artery Calcium in Patients Receiving Computed Tomography Pulmonary Angiography for Suspected Pulmonary Embolism in the Emergency Department.

PURPOSE: Coronary artery calcium (CAC) is a frequent incidental finding on computed tomography pulmonary angiogram (CTPA) in the evaluation of pulmonary embolism (PE) in the emergency department (ED); however, its prognostic value is unclear. In this study, we interrogate the prognostic value of CAC identified on CTPA in predicting adverse outcomes in the evaluation of PE in the ED. MATERIALS AND METHODS: In this retrospective cohort study, we identified 610 patients presenting to the ED in 2013 and evaluated with CTPA for suspected PE. Ordinal CAC scores were evaluated as absent (0), mild (1), moderate (2), or severe (3) in each of the 4 main coronary arteries. Composite CAC scores were subsequently compared against adverse clinical outcomes, defined as intensive care unit admission, hospital stay longer than 72 hours, or death during hospital course or at 6-month follow-up, using univariate and multivariate logistic regression analyses. Relevant exclusion criteria included a history of cardiovascular disease. RESULTS: In all, 365 patients met the inclusion criteria (231 women, mean age 56±16 y) with 132 patients (36%) having some degree of CAC and 16 (4%) having severe CAC. Known malignancy was present in 151 (41%) patients and composite adverse clinical outcomes were observed in 98 patients (32%). Age, presence of acute PE, malignancy, and presence of CAC were significant predictors of adverse outcomes on both univariate and multivariate analyses. CAC was not an independent predictor of short-term adverse outcomes on multivariate analysis ( P =0.06) when all patients were considered. However, when patients with known malignancy were excluded, CAC was an independent predictor of short-term adverse outcomes (odds ratio=2.5, confidence interval=1.1-5.5, P =0.03) independent of age and presence of PE. CONCLUSION: The presence of CAC on CT PA was predictive of adverse outcomes in patients without known cardiac disease presenting to the ED with suspected PE.

Semi-automated analysis of 4D flow MRI to assess the hemodynamic impact of intracranial atherosclerotic disease.

PURPOSE: This study evaluated the feasibility of using 4D flow MRI and a semi-automated analysis tool to assess the hemodynamic impact of intracranial atherosclerotic disease (ICAD). The ICAD impact was investigated by evaluating pressure drop (PD) at the atherosclerotic stenosis and changes in cerebral blood flow distribution in patients compared to healthy controls. METHODS: Dual-venc 4D flow MRI was acquired in 25 healthy volunteers and 16 ICAD patients (ICA, N = 3; MCA, N = 13) with mild (<50%), moderate (50-69%), or severe (>70%) intracranial stenosis. A semi-automated analysis tool was developed to quantify velocity and flow from 4D flow MRI and to evaluate cerebral blood flow redistribution. PD at stenosis was estimated using the Bernoulli equation. The PD calculation was examined by an in vitro phantom study against flow simulations. RESULTS: Flow analysis in controls indicated symmetry in blood flow rate (FR) and peak velocity (PV) between the brain hemispheres. For patients, PV in the affected hemisphere was significantly (65%) higher than the normal side (P = 0.002). However, FR to both hemispheres of the brain was the same. The PD depicted significant correlation with PV asymmetry in patients (ρ = 0.67 and P = 0.02), and it was significantly higher for severe compared to moderate stenosis (3.73 vs. 2.30 mm Hg, P = 0.02). CONCLUSION: 4D flow MRI quantification enables assessment of the hemodynamic impact of ICAD. The significant difference of the PD between patients with severe and moderate stenosis and its correlation with PV asymmetry suggest that PD may be a pertinent hemodynamic biomarker to evaluate ICAD.

Diffusion-compensated tofts model suggests contrast leakage through aneurysm wall.

PURPOSE: The purpose of this study was to investigate the diffusional transport of contrast agent and its effects on kinetic modeling of dynamic contrast enhanced (DCE) images. METHODS: We performed simulations of our diffusion-compensated model and compared these results to human intracranial aneurysms (IAs). We derive an easy-to-use parameterization of diffusional effects that can provide an accurate estimate of diffusion corrected contrast agent leakage rates (ktrans ). Finally, we performed re-ansalysis of an existing data set to determine whether diffusion-corrected kinetic parameters improve the identification of high-risk IAs, thereby providing a new MRI-based imaging metric of IA stability based on wall integrity. RESULTS: Probability distributions of simulated versus measured data show contrast leakage away from the aneurysm wall. Parameterization of diffusional effects on ktrans showed high correlation with long-chain methods in both surrounding tissue and near the aneurysm wall (r2 = 0.91 and r2 = 0.90, respectively). Finally, size, ktrans , and ( ktrans-kDCtrans) showed significant univariate relationships with rupture risk (P < 0.05). CONCLUSIONS: We report the first evidence of diffusion-compensated permeability modeling in intracranial aneurysms and propose a parameterization of diffusional effects on ktrans . Furthermore, a comparison of measured versus simulated data suggests that contrast leakage occurs across the aneurysm wall. Magn Reson Med 78:2388-2398, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Automated analysis of perfusion weighted MRI using asymmetry in vascular territories.

PURPOSE: To determine the feasibility of automatic vascular territory region of interest (ROI) construction as a method for standardized quantification of cerebral blood flow (CBF) images. MATERIALS AND METHODS: An algorithm for automatic construction of vascular territory ROIs was performed on 10 healthy controls and 25 patients with perfusion abnormalities identified by retrospective chart review. The ROIs were used to quantify perfusion asymmetry for each territory, and perfusion asymmetry was compared in the two cohorts and against blinded neuroradiologist interpretation. The algorithm was additionally applied to a separate cohort of 23 prospectively enrolled patients and perfusion asymmetry was correlated against clinical variables. RESULTS: There was significantly greater perfusion asymmetry in territories graded by neuroradiologists as hypoperfused compared to those graded as normally perfused (p<.05) and compared to healthy volunteers (p<.01). An ROC analysis showed that perfusion asymmetry was sensitive and specific for identifying hypoperfusion in vascular territories (84.9% sensitivity and 90.5% specificity for a threshold asymmetry index of .829). In the prospective cohort, perfusion asymmetry was correlated with initial NIH stroke scale (NIHSS) (p<.01) and length of stay (p<.05). CONCLUSIONS: Automatic construction of vascular territory ROIs and calculation of perfusion asymmetry is a feasible method for analyzing CBF images. Because the technique is rapid and minimizes bias, it can facilitate analysis of larger scale research studies.

Snapshot MR technique to measure OEF using rapid frequency mapping.

Magnetic resonance (MR)-based oxygen extraction fraction (OEF) measurement techniques that use blood oxygen level-dependent (BOLD)-based approaches require the measurement of the R2' decay rate and deoxygenated blood volume to derive the local oxygen saturation in vivo. We describe here a novel approach to measure OEF using rapid local frequency mapping. By modeling the MR decay process in the static dephasing regime as two separate dissipative and oscillatory effects, we calculate the OEF from local frequencies measured across the brain by assuming that the biophysical mechanisms causing OEF-related frequency changes can be determined from the oscillatory effects. The Parameter Assessment by Retrieval from Signal Encoding (PARSE) technique was used to acquire the local frequency change maps. The PARSE images were taken on 11 normal volunteers, and 1 patient exhibiting hemodynamic stress. The mean MR-OEF in 11 normal subjects was 36.66±7.82%, in agreement with positron emission tomography (PET) literature. In regions of hemodynamic stress induced by vascular steal, OEF exhibits the predicted focal increases. These preliminary results show that it is possible to measure OEF using a rapid frequency mapping technique. Such a technique has numerous advantages including speed of acquisition, is noninvasive, and has sufficient spatial and temporal resolution.

RAZER: a pulse sequence for whole-brain bolus tracking at high frame rates.

PURPOSE: To introduce a pulse sequence that obtains whole-brain perfusion measurements at 1.7 mm isotropic voxel resolution by dynamic susceptibility contrast MRI bolus tracking despite using a temporal resolution of 10.3 s: RAdial kZ-blipped 3D GRE-echo-planar imaging (GRE-EPI) for whole-brain pERfusion (RAZER). METHODS: In RAZER, in-plane radial and through-plane 3D GRE-EPI Cartesian sampling was used to produce a 3D stack-of-stars k-space. In vivo scans on one healthy volunteer and one patient with Moyamoya disease were performed using RAZER and a typical 2D GRE-EPI pulse sequence as a reference standard. Agreement in perfusion metrics was reported using linear regression analysis and Bland-Altman plots. RESULTS: Sliding window reconstruction recovered dynamic information lost in the large temporal acquisition window of RAZER. Inline phase correction scans corrected N/2 ghosting artifacts and view-dependent phase variations. Whole-brain images of cerebral blood volume, cerebral blood flow, and mean transit time were calculated with RAZER at 1.7 mm isotropic voxel resolution and good reference standard agreement in both subjects when sliding window reconstruction was used (r(2) > 0.7, mean bias in mean transit time measurements < 0.5 s). CONCLUSIONS: Despite using a temporal resolution of 10.3 s, in vivo data indicates that RAZER is able to obtain whole-brain perfusion measurements at 1.7 mm isotropic voxel resolution and good reference standard agreement.

Three-dimensional hemodynamics in intracranial aneurysms: influence of size and morphology.

PURPOSE: To use four-dimensional (4D)-flow MRI for the comprehensive in vivo analysis of hemodynamics and its relationship to size and morphology of different intracranial aneurysms (IA). We hypothesize that different IA groups, defined by size and morphology, exhibit different velocity fields, wall shear stress, and vorticity. MATERIALS AND METHODS: The 4D-flow MRI (spatial resolution = 0.99-1.8 × 0.78-1.46 × 1.2-1.4 mm(3) , temporal resolution = 44-48 ms) was performed in 19 IAs (18 patients, age = 55.4 ± 13.8 years) with saccular (n = 16) and fusiform (n = 3) morphology and different sizes ranging from small (n = 8; largest dimension = 6.2 ± 0.4 mm) to large and giant (n = 11; 25 ± 7 mm). Analysis included quantification of volumetric spatial-temporal velocity distribution, vorticity, and wall shear stress (WSS) along the aneurysm's 3D surface. RESULTS: The 4D-flow MRI revealed distinct hemodynamic patterns for large/giant saccular aneurysms (Group 1), small saccular aneurysms (Group 2), and large/giant fusiform aneurysms (Group 3). Saccular IA (Groups 1, 2) demonstrated significantly higher peak velocities (P < 0.002) and WSS (P < 0.001) compared with fusiform aneurysms. Although intra-aneurysmal 3D velocity distributions were similar for Group 1 and 2, vorticity and WSS was significantly (P < 0.001) different (increased in Group 1 by 54%) indicating a relationship between IA size and hemodynamics. Group 3 showed reduced velocities (P < 0.001) and WSS (P < 0.001). CONCLUSION: The 4D-flow MRI demonstrated the influence of lesion size and morphology on aneurysm hemodynamics suggesting the potential of 4D-flow MRI to assist in the classification of individual aneurysms.

Cerebrovascular occlusive disease: quantitative cerebral blood flow using dynamic susceptibility contrast mr imaging correlates with quantitative H2[15O] PET.

PURPOSE: To compare quantitative values of cerebral blood flow (CBF) derived from dynamic susceptibility contrast (DSC) magnetic resonance (MR) imaging with reference standard positron emission tomography (PET) in patients with confirmed cerebrovascular occlusive disease. MATERIALS AND METHODS: Local institutional review board approval and informed consent were obtained for a prospective study of 18 patients (six men, 12 women; age range, 28-71 years; mean age, 45 years ± 10.4 [standard deviation]) with angiographically confirmed Moyamoya (n = 8) or internal carotid artery occlusions (n = 10). DSC MR images and oxygen 15-labeled water (H(2)[(15)O]) PET images were acquired on the same day. DSC images were postprocessed to yield parametric images of CBF (in mL/100 g/min), coregistered, and analyzed using grid-based regions of interest. Mean values of CBF in each region of interest from MR imaging and PET data sets were compared. Correlations for each patient were determined and overall agreement between pooled MR imaging and PET CBF was reported using linear regression analysis and Bland-Altman plots. RESULTS: Strong correlations (r(2) ≥ 0.55) were found between MR imaging and PET CBF values in all patients. Use of the bookend approach was found to underestimate CBF predictably across the patient cohort (mean slope, 0.82; standard deviation, 0.18; slope of aggregated data, 0.75). This allowed for a simple rescaling of MR imaging values producing strong agreement with PET values in the aggregated data (r(2) = 0.66; slope = 1.00; intercept = 0.00). CONCLUSION: The data show that the bookend MR imaging technique produces similar results for quantitative CBF between DSC MR imaging and H(2)[(15)O] PET. Although MR-derived CBF underestimated PET-derived CBF, the patient-to-patient variability in the slopes of the linear MR and PET relationships was significantly smaller than a competing quantitation technique. As a result, the bookend technique appears to more predictably measure quantitative CBF in a clinical setting.

Combined renal MRA and perfusion with a single dose of contrast.

Both anatomical and functional scans are often performed when diagnosing renovascular diseases, which in many cases require two separate contrast injections. With nephrogenic systemic fibrosis being associated with gadolinium, minimizing contrast injection dosage is desirable. In this study, a technique which performs time-resolved renal magnetic resonance angiography (MRA) and perfusion with a single scan and single dose of contrast has been evaluated in six healthy volunteers. A previously developed three-dimensional MRA technique called Contrast-enhanced Angiography with Multi-Echo and Radial k-space (CAMERA) has been used to acquire images, and perfusion analysis was performed using deconvolution methods. Time-resolved MRA, as well as renal blood flow, renal volume of distribution and mean transit time maps, were acquired.

Magnetization spoiling in radial FLASH contrast-enhanced MR digital subtraction angiography.

PURPOSE: To increase the in-plane spatial resolution and image update rates of 2D magnetic resonance (MR) digital subtraction angiography (DSA) pulse sequences to 0.57 × 0.57 mm and 6 frames/sec, respectively, for intracranial vascular disease applications by developing a radial FLASH protocol and to characterize a new artifact, not previously described in the literature, which arises in the presence of such pulse sequences. MATERIALS AND METHODS: The pulse sequence was optimized and artifacts were characterized using simulation and phantom studies. With Institutional Review Board (IRB) approval, the pulse sequence was used to acquire time-resolved images from healthy human volunteers and patients with x-ray DSA-confirmed intracranial vascular disease. RESULTS: Artifacts were shown to derive from inhomogeneous spoiling due to the nature of radial waveforms. Gradient spoiling strategies were proposed to eliminate the observed artifact by balancing gradient moments across TR intervals. The resulting radial 2D MR DSA sequence (2.6 sec temporal footprint, 6 frames/sec with sliding window factor 16, 0.57 × 0.57 mm in-plane) demonstrated small vessel detail and corroborated x-ray DSA findings in intracranial vascular imaging studies. CONCLUSION: Appropriate gradient spoiling in radial 2D MR DSA pulse sequences improves intracranial vascular depiction by eliminating circular banding artifacts. The proposed pulse sequence may provide a useful addition to clinically applied 2D MR DSA scans.

Correction for arterial-tissue delay and dispersion in absolute quantitative cerebral perfusion DSC MR imaging.

The singular value decomposition deconvolution of cerebral tissue concentration-time curves with the arterial input function is commonly used in dynamic susceptibility contrast cerebral perfusion MR imaging. However, it is sensitive to the time discrepancy between the arrival of the bolus in the tissue concentration-time curve and the arterial input function signal. This normally causes inaccuracy in the quantitative perfusion maps due to delay and dispersion effects. A comprehensive correction algorithm has been achieved through slice-dependent time-shifting of the arterial input function, and a delay-dependent dispersion correction model. The correction algorithm was tested in 11 healthy subjects and three ischemic stroke patients scanned with a quantitative perfusion pulse sequence at 1.5 T. A validation study was performed on five patients with confirmed cerebrovascular occlusive disease scanned with MRI and positron emission tomography at 3.0 T. A significant effect (P < 0.05) was reported on the quantitative cerebral blood flow and mean transit time measurements (up to 50%). There was no statistically significant effect on the quantitative cerebral blood volume values. The in vivo results were in agreement with the simulation results, as well as previous literature. This minimizes the bias in patient diagnosis due to the existing errors and artifacts in dynamic susceptibility contrast imaging.

Time-resolved magnetic resonance angiography: evaluation of intrapulmonary circulation parameters in pulmonary arterial hypertension.

PURPOSE: To determine whether pulmonary arterial and venous transit times measured by time-resolved magnetic resonance angiography (MRA) can be used as a diagnostic tool for pulmonary arterial hypertension (PAH). MATERIALS AND METHODS: Twelve patients with confirmed PAH and 10 healthy volunteers were scanned with Institutional Review Board (IRB) approval. Time-resolved MRA and 2D phase contrast flow images of the pulmonary vasculature were acquired. Pulmonary arterial and venous transit times (PaTT and PvTT) and pulmonary valve flow (PVF) were obtained. Pulmonary arterial and pulmonary venous blood volumes (PaBV and PvBV) were calculated as the product of flow and transit time. RESULTS: Patients with PAH showed statistically significant increases in PaTT and PvTT (P < 0.0004, P < 0.05, respectively) compared to controls. PaBV (165.2 ± 92.0 mL) was significantly higher in PAH subjects than controls (97.0 ± 47.1 mL) (P < 0.04), whereas PvBV (127.9 ± 148.9 mL) of PAH subjects had no significant increase from those of healthy controls (142.5 ± 104.1 mL) (P < 0.38). CONCLUSION: Pulmonary arterial transit times measured using time-resolved MRA can be used as a simple, noninvasive metric for detection of altered hemodynamics in PAH.

Spectroscopic microvascular blood detection from the endoscopically normal colonic mucosa: biomarker for neoplasia risk.

BACKGROUND & AIMS: We previously used a novel biomedical optics technology, 4-dimensional elastically scattered light fingerprinting, to show that in experimental colon carcinogenesis the predysplastic epithelial microvascular blood content is increased markedly. To assess the potential clinical translatability of this putative field effect marker, we characterized the early increase in blood supply (EIBS) in human beings in vivo. METHODS: We developed a novel, endoscopically compatible, polarization-gated, spectroscopic probe that was capable of measuring oxygenated and deoxygenated (Dhb) hemoglobin specifically in the mucosal microcirculation through polarization gating. Microvascular blood content was measured in 222 patients from the endoscopically normal cecum, midtransverse colon, and rectum. If a polyp was present, readings were taken from the polyp tissue along with the normal mucosa 10-cm and 30-cm proximal and distal to the lesion. RESULTS: Tissue phantom studies showed that the probe had outstanding accuracy for hemoglobin determination (r(2) = 0.99). Augmentation of microvasculature blood content was most pronounced within the most superficial ( approximately 100 microm) layer and dissipated in deeper layers (ie, submucosa). EIBS was detectable within 30 cm from the lesion and the magnitude mirrored adenoma proximity. This occurred for both oxygenated hemoglobin and DHb, with the effect size being slightly greater for DHb. EIBS correlated with adenoma size and was not engendered by nonneoplastic (hyperplastic) polyps. CONCLUSIONS: We show, herein, that in vivo microvascular blood content can be measured and provides an accurate marker of field carcinogenesis. This technological/biological advance has numerous potential applications in colorectal cancer screening such as improved polyp detection and risk stratification.