Quantitative assessment of microvasculopathy in arcAβ mice with USPIO-enhanced gradient echo MRI.
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ABSTRACT:
SUBMITTER: Klohs J
PROVIDER: S-EPMC5010097 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In various cancer types, the first step towards extended metastatic disease is the presence of lymph node metastases. Imaging methods with sufficient diagnostic accuracy are required to personalize treatment. Lymph node metastases can be detected with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI), but this method needs validation. Here, a workflow is presented, which is designed to compare MRI-visible lymph nodes on a node-to-node basis with histopathology. In patients with prostate, rectal, periampullary, esophageal, and head-and-neck cancer, in vivo USPIO-enhanced MRI was performed to detect lymph nodes suspicious of harboring metastases. After lymphadenectomy, but before histopathological assessment, a 7 Tesla preclinical ex vivo MRI of the surgical specimen was performed, and in vivo MR images were radiologically matched to ex vivo MR images. Lymph nodes were annotated on the ex vivo MRI for an MR-guided pathological examination of the specimens. Matching lymph nodes of ex vivo MRI to pathology was feasible in all cancer types. The annotated ex vivo MR images enabled a comparison between USPIO-enhanced in vivo MRI and histopathology, which allowed for analyses on a nodal, or at least on a nodal station, basis. A workflow was developed to validate in vivo USPIO-enhanced MRI with histopathology. Guiding the pathologist towards lymph nodes in the resection specimens during histopathological work-up allowed for the analysis at a nodal basis, or at least nodal station basis, of in vivo suspicious lymph nodes with corresponding histopathology, providing direct information for validation of in vivo USPIO-enhanced, MRI-detected lymph nodes.
| S-EPMC8938816 | biostudies-literature
Project description:There is an urgent need for better detection and understanding of vascular abnormalities at the micro-level, where critical vascular nourishment and cellular metabolic changes occur. This is especially the case for structures such as the midbrain where both the feeding and draining vessels are quite small. Being able to monitor and diagnose vascular changes earlier will aid in better understanding the etiology of the disease and in the development of therapeutics. In this work, thirteen healthy volunteers were scanned with a dual echo susceptibility weighted imaging (SWI) sequence, with a resolution of 0.22 × 0.44 × 1 mm3 at 3T. Ultra-small superparamagnetic iron oxides (USPIO) were used to induce an increase in susceptibility in both arteries and veins. Although the increased vascular susceptibility enhances the visibility of small subvoxel vessels, the accompanying strong signal loss of the large vessels deteriorates the local tissue contrast. To overcome this problem, the SWI data were acquired at different time points during a gradual administration (final concentration = 4 mg/kg) of the USPIO agent, Ferumoxytol, and the data was processed to combine the SWI data dynamically, in order to see through these blooming artifacts. The major vessels and their tributaries (such as the collicular artery, peduncular artery, peduncular vein and the lateral mesencephalic vein) were identified on the combined SWI data using arterio-venous maps. Dynamically combined SWI data was then compared with previous histological work to validate that this protocol was able to detect small vessels on the order of 50 μm-100 μm. A complex division-based phase unwrapping was also employed to improve the quality of quantitative susceptibility maps by reducing the artifacts due to aliased voxels at the vessel boundaries. The smallest detectable vessel size was then evaluated by revisiting numerical simulations, using estimated true susceptibilities for the basal vein and the posterior cerebral artery in the presence of Ferumoxytol. These simulations suggest that vessels as small as 50 μm should be visible with the maximum dose of 4 mg/kg.
| S-EPMC9401191 | biostudies-literature
Project description:PurposeTo develop a method to reconstruct quantitative susceptibility mapping (QSM) from multi-echo, multi-flip angle data collected using strategically acquired gradient echo (STAGE) imaging.MethodsThe proposed QSM reconstruction algorithm, referred to as "structurally constrained Susceptibility Weighted Imaging and Mapping" scSWIM, performs an ℓ 1 and ℓ 2 regularization-based reconstruction in a single step. The unique contrast of the T1 weighted enhanced (T1WE) image derived from STAGE imaging was used to extract reliable geometry constraints to protect the basal ganglia from over-smoothing. The multi-echo multi-flip angle data were used for improving the contrast-to-noise ratio in QSM through a weighted averaging scheme. The measured susceptibility values from scSWIM for both simulated and in vivo data were compared to the: original susceptibility model (for simulated data only), the multi orientation COSMOS (for in vivo data only), truncated k-space division (TKD), iterative susceptibility weighted imaging and mapping (iSWIM), and morphology enabled dipole inversion (MEDI) algorithms. Goodness of fit was quantified by measuring the root mean squared error (RMSE) and structural similarity index (SSIM). Additionally, scSWIM was assessed in ten healthy subjects.ResultsThe unique contrast and tissue boundaries from T1WE and iSWIM enable the accurate definition of edges of high susceptibility regions. For the simulated brain model without the addition of microbleeds and calcium, the RMSE was best at 5.21ppb for scSWIM and 8.74ppb for MEDI thanks to the reduced streaking artifacts. However, by adding the microbleeds and calcium, MEDI's performance dropped to 47.53ppb while scSWIM performance remained the same. The SSIM was highest for scSWIM (0.90) and then MEDI (0.80). The deviation from the expected susceptibility in deep gray matter structures for simulated data relative to the model (and for the in vivo data relative to COSMOS) as measured by the slope was lowest for scSWIM + 1%(-1%); MEDI + 2%(-11%) and then iSWIM -5%(-10%). Finally, scSWIM measurements in the basal ganglia of healthy subjects were in agreement with literature.ConclusionThis study shows that using a data fidelity term and structural constraints results in reduced noise and streaking artifacts while preserving structural details. Furthermore, the use of STAGE imaging with multi-echo and multi-flip data helps to improve the signal-to-noise ratio in QSM data and yields less artifacts.
| S-EPMC7645168 | biostudies-literature
Project description:PurposeTo evaluate the technical feasibility of high-resolution USPIO-enhanced magnetic resonance imaging of pelvic lymph nodes (LNs) at ultrahigh magnetic field strength.Materials and methodsThe ethics review board approved this study and written informed consent was obtained from all patients. Three patients with rectal cancer and three selected patients with (recurrent) prostate cancer were examined at 7-T 24-36 h after intravenous ferumoxtran-10 administration; rectal cancer patients also received a 3-T MRI. Pelvic LN imaging was performed using the TIAMO technique in combination with water-selective multi-GRE imaging and lipid-selective GRE imaging with a spatial resolution of 0.66 × 0.66 × 0.66mm3. T2*-weighted images of the water-selective imaging were computed from the multi-GRE images at TE = 0, 8, and 14 ms and used for the assessment of USPIO uptake.ResultsHigh-resolution 7-T MR gradient-echo imaging was obtained robustly in all patients without suffering from RF-related signal voids. USPIO signal decay in LNs was visualized using computed TE imaging at TE = 8 ms and an R2* map derived from water-selective imaging. Anatomically, LNs were identified on a combined reading of computed TE = 0 ms images from water-selective scans and images from lipid-selective scans. A range of 3-48 LNs without USPIO signal decay was found per patient. These LNs showed high signal intensity on computed TE = 8 and 14 ms imaging and low R2* (corresponding to high T2*) values on the R2* map.ConclusionUSPIO-enhanced MRI of the pelvis at 7-T is technically feasible and offers opportunities for detecting USPIO uptake in normal-sized LNs, due to its high intrinsic signal-to-noise ratio and spatial resolution.Key points• USPIO-enhanced MRI at 7-T can indicate USPIO uptake in lymph nodes based on computed TE images. • Our method promises a high spatial resolution for pelvic lymph node imaging.
| S-EPMC6828641 | biostudies-literature
Project description:PurposeConventional MRI using contrast agents is semiquantitative because it is inherently sensitive to extravoxular susceptibility artifacts, field inhomogeneity, partial voluming, perivascular effects, and motion/flow artifacts. Herein we demonstrate a quantitative contrast-enhanced MRI technique using ultrashort time-to-echo pulse sequences for measuring clinically relevant concentrations of ferumoxytol, a superparamagnetic iron oxide nanoparticle contrast agent with high sensitivity and precision in vitro and in vivo.MethodsThe method achieves robust, reproducible results by using rapid signal acquisition at ultrashort time-to-echo (UTE) to produce positive contrast images with pure T1 weighting and little T2* decay. The spoiled gradient echo equation is used to transform UTE intensities directly into concentration using experimentally determined relaxivity constants and image acquisition parameters.ResultsA multiparametric optimization of acquisition parameters revealed an optimal zone capable of producing high-fidelity measurements. Clinically relevant intravascular concentrations of ferumoxytol were measured longitudinally in mice with high sensitivity and precision (∼7.1% error). MRI measurements were independently validated by elemental iron analysis of sequential blood draws. Automated segmentation of ferumoxytol concentration yielded high quality three-dimensional images for visualization of perfusion.ConclusionsThis ability to longitudinally quantify blood pool CA concentration is unique to quantitative UTE contrast-enhanced (QUTE-CE) MRI and makes QUTE-CE MRI competitive with nuclear imaging.
| S-EPMC6691359 | biostudies-literature
Project description:BackgroundImaging biomarkers of progressive multiple sclerosis (MS) are needed. Quantitative gradient recalled echo (qGRE) magnetic resonance imaging (MRI) evaluates microstructural tissue damage in MS.ObjectiveTo evaluate qGRE-derived R2t* as an imaging biomarker of MS progression compared with atrophy and lesion burden.MethodsTwenty-three non-relapsing progressive MS (PMS), 22 relapsing-remitting MS (RRMS), and 18 healthy control participants underwent standard MS physical and cognitive neurological assessments and imaging with qGRE, FLAIR, and MPRAGE at 3T. PMS subjects were tested clinically and imaged every 9 months over 45 months. Imaging measures included lesion burden, atrophy, and R2t* in cortical gray matter (GM), deep GM, and normal-appearing white matter (NAWM). Longitudinal analysis of clinical performance and imaging biomarkers in PMS subjects was conducted via linear models with subject as repeated, within-subject factor. Relationship between imaging biomarkers and clinical scores was assessed by Spearman rank correlation.ResultsR2t* reductions correlated with neurological impairment cross-sectionally and longitudinally. PMS patients with clinically defined disease progression (N = 13) showed faster decrease of R2t* in NAWM and deep GM compared with the clinically stable PMS group (N = 10). Importantly, tissue damage measured by R2t* outperformed lesion burden and atrophy as a biomarker of progression during the study period.ConclusionqGRE-derived R2t* is a potential imaging biomarker of MS progression.
| S-EPMC9329152 | biostudies-literature
Project description:A protocol for evaluating ultrasmall superparamagnetic particles of iron oxide (USPIO) uptake and elimination in cerebral small vessel disease patients was developed and piloted. B₁-insensitive R₁ measurement was evaluated in vitro. Twelve participants with history of minor stroke were scanned at 3-T MRI including structural imaging, and R₁ and R₂* mapping. Participants were scanned (i) before and (ii) after USPIO (ferumoxytol) infusion, and again at (iii) 24⁻30 h and (iv) one month. Absolute and blood-normalised changes in R₁ and R₂* were measured in white matter (WM), deep grey matter (GM), white matter hyperintensity (WMH) and stroke lesion regions. R₁ measurements were accurate across a wide range of values. R₁ (p < 0.05) and R₂* (p < 0.01) mapping detected increases in relaxation rate in all tissues immediately post-USPIO and at 24⁻30 h. R₂* returned to baseline at one month. Blood-normalised R₁ and R₂* changes post-infusion and at 24⁻30 h were similar, and were greater in GM versus WM (p < 0.001). Narrower distributions were seen with R₂* than for R₁ mapping. R₁ and R₂* changes were correlated at 24⁻30 h (p < 0.01). MRI relaxometry permits quantitative evaluation of USPIO uptake; R₂* appears to be more sensitive to USPIO than R₁. Our data are explained by intravascular uptake alone, yielding estimates of cerebral blood volume, and did not support parenchymal uptake. Ferumoxytol appears to be eliminated at 1 month. The approach should be valuable in future studies to quantify both blood-pool USPIO and parenchymal uptake associated with inflammatory cells or blood-brain barrier leak.
| S-EPMC6387454 | biostudies-literature
Project description:PurposeA method named DECOMPOSE-QSM is developed to decompose bulk susceptibility measured with QSM into sub-voxel paramagnetic and diamagnetic components based on a three-pool complex signal model.MethodsMulti-echo gradient echo signal is modeled as a summation of three weighted exponentials corresponding to three types of susceptibility sources: reference susceptibility, diamagnetic and paramagnetic susceptibility relative to the reference. Paramagnetic component susceptibility (PCS) and diamagnetic component susceptibility (DCS) maps are constructed to represent the sub-voxel compartments by solving for linear and nonlinear parameters in the model.ResultsNumerical forward simulation and phantom validation confirmed the ability of DECOMPOSE-QSM to separate the mixture of paramagnetic and diamagnetic components. The PCS obtained from temperature-variant brainstem imaging follows the Curie's Law, which further validated the model and the solver. Initial in vivo investigation of human brain images showed the ability to extract sub-voxel PCS and DCS sources that produce visually enhanced contrast between brain structures comparing to threshold QSM.
| S-EPMC8720043 | biostudies-literature
Project description:Recent studies have shown that there is a direct link between the orientation of the nerve fibers in white matter (WM) and the contrast observed in magnitude and phase images acquired using gradient echo MRI. Understanding the origin of this link is of great interest because it could offer access to a new diagnostic tool for investigating tissue microstructure. Since it has been suggested that myelin is the dominant source of this contrast, creating an accurate model for characterizing the effect of the myelin sheath on the evolution of the NMR signal is an essential step toward fully understanding WM contrast. In this study, we show by comparison of the results of simulations and experiments carried out on human subjects at 7T, that the magnitude and phase of signals acquired from WM in vivo can be accurately characterized by (i) modeling the myelin sheath as a hollow cylinder composed of material having an anisotropic magnetic susceptibility that is described by a tensor with a radially oriented principal axis, and (ii) adopting a two-pool model in which the water in the sheath has a reduced T(2) relaxation time and spin density relative to its surroundings, and also undergoes exchange. The accuracy and intrinsic simplicity of the hollow cylinder model provides a versatile framework for future exploitation of the effect of WM microstructure on gradient echo contrast in clinical MRI.
| S-EPMC3494918 | biostudies-literature
Project description:Background Myocardial oxygenation imaging could help determine the presence of microvascular dysfunction associated with increased cardiovascular risk. However, it is challenging to depict the potentially small oxygenation alterations with current noninvasive cardiac MRI blood oxygen level-dependent (BOLD) techniques. Purpose To demonstrate the cardiac application of a gradient-echo spin-echo (GESE) echo-planar imaging sequence for dynamic and quantitative heartbeat-to-heartbeat BOLD MRI and evaluate the sequence in populations both healthy and with hypertension in combination with a breath hold-induced CO2 intervention. Materials and Methods GESE echo-planar imaging sequence was performed in 18 healthy participants and in eight prospectively recruited participants with hypertension on a 3.0-T MRI system. T2 and T2* maps were calculated per heartbeat with a four-parameter fitting technique. Septal regions of interests were used to determine T2 and T2* values per heartbeat and examined over the course of a breath hold to determine BOLD changes. T2 and T2* changes of healthy participants and participants with hypertension were compared by using a nonparametric Mann-Whitney test. Results GESE echo-planar imaging approach gave spatially stable T2 and T2* maps per heartbeat for healthy participants and participants with hypertension, with mean T2 values of 43 msec ± 5 (standard deviation) and 46 msec ± 9, respectively, and mean T2* values of 28 msec ± 5 and 22 msec ± 5, respectively. The healthy participants exhibited increasing T2 and T2* values over the course of a breath hold with a mean positive slope of 0.2 msec per heartbeat ± 0.1 for T2 and 0.2 msec per heartbeat ± 0.1 for T2*, whereas for participants with hypertension these dynamic T2 and T2* values had a mean negative slope of -0.2 msec per heartbeat ± 0.2 for T2 and -0.1 msec per heartbeat ± 0.2 for T2*. The difference in these mean slopes between healthy participants and participants with hypertension was significant for both T2 (P < .001) and T2* (P < .001). Conclusion Gradient-echo spin-echo echo-planar imaging sequence provided quantitative T2 and T2* maps per heartbeat and enabled dynamic heartbeat-to-heartbeat blood oxygen level-dependent (BOLD)-response imaging by analyzing changes in T2 and T2* over the time of a breath-hold intervention. This approach could identify differences in the BOLD response between healthy participants and participants with hypertension. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Friedrich in this issue.
| S-EPMC7053244 | biostudies-literature