Reduced oxygen extraction fraction in deep cerebral veins associated with cognitive impairment in multiple sclerosis.

Studying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS). This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients. Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (SvO2) in the ICVs. Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of SvO2 (74.5 ± 1.89% vs 72.4 ± 2.23%) in patients with RRMS compared with age- and sex-matched healthy controls. Both the susceptibility of ICVs (r = 0.508, p = 0.031) and the SvO2 (r = -0.498, p = 0.036) exhibited a moderate correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale. The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS. .

The STRAT-PARK cohort: A personalized initiative to stratify Parkinson's disease.

The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson's disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms. Molecular stratification and identification of disease subtypes is therefore a key priority for understanding and treating PD. STRAT-PARK is a multi-center longitudinal cohort aiming to recruit a total of 2000 individuals with PD and neurologically healthy controls from Norway and Canada, for the purpose of identifying molecular disease subtypes. Clinical assessment is performed annually, whereas biosampling, imaging, and digital and neurophysiological phenotyping occur every second year. The unique feature of STRAT-PARK is the diversity of collected biological material, including muscle biopsies and platelets, tissues particularly useful for mitochondrial biomarker research. Recruitment rate is ∼150 participants per year. By March 2023, 252 participants were included, comprising 204 cases and 48 controls. STRAT-PARK is a powerful stratification initiative anticipated to become a global research resource, contributing to personalized care in PD.

Vascular Aging in the Choroid Plexus: A 7T Ultrasmall Superparamagnetic Iron Oxide (USPIO)-MRI Study.

BACKGROUND: The choroid plexus (ChP), a densely vascularized structure, has drawn increasing attention for its involvement in brain homeostasis and waste clearance. While the volumetric changes have been explored in many imaging studies, few studies have investigated the vascular degeneration associated with aging in the ChP. PURPOSE: To investigate the sub-structural characteristics of the ChP, particularly the vascular compartment using high-resolution 7T imaging enhanced with Ferumoxytol, an ultrasmall super-paramagnetic iron oxide, which greatly increase the susceptibility contrast for vessels. STUDY TYPE: Prospective. SUBJECTS: Forty-nine subjects without neurological disorders (age: 21-80 years; 42 ± 17 years; 20 females). FIELD STRENGTH/SEQUENCE: 7-T with 2D and 3D T2* GRE, 3D MPRAGE T1, 2D TSE T2, and 2D FLAIR. ASSESSMENT: The vascular and stromal compartments of the ChP were segmented using K-means clustering on post-contrast 2D GRE images. Visual and qualitative assessment of ChP vascular characteristics were conducted independently by three observers. Vascular density (Volvessel/VolChP ratio) and susceptibility change (Δχ) induced by Ferumoxytol were analyzed on 3D GRE-derived susceptibility-weighted imaging and quantitative susceptibility mapping, respectively. STATISTICAL TESTS: Independent t-test, Mann-Whitney U test, and Chi-square test were utilized for group comparisons. The relationship between age and ChP's vascular alterations was examined using Pearson's correlation. Intra-class coefficient was calculated for inter-observer agreement. A P value <0.05 was considered statistically significant. RESULTS: 2D GRE images demonstrated superior contrast and accurate delineation of ChP substructures (ICC = 0.86). Older subjects exhibited a significantly smaller vascular density (16.5 ± 4.34%) and lower Δχ (22.10 ± 12.82 ppb) compared to younger subjects (24.85 ± 6.84% and 34.64 ± 12.69 ppb). Vascular density and mean Δχ within the ChP negatively correlated with age (r = -0.48, and r = -0.45). DATA CONCLUSION: Ferumoxytol-enhanced 7T images can demonstrate ChP alterations in elderly with decreased vascular density and expansion of nonvascular compartment. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

In vivo mapping of hippocampal venous vasculature and oxygenation using susceptibility imaging at 7T.

Mapping the small venous vasculature of the hippocampus in vivo is crucial for understanding how functional changes of hippocampus evolve with age. Oxygen utilization in the hippocampus could serve as a sensitive biomarker for early degenerative changes, surpassing hippocampal tissue atrophy as the main source of information regarding tissue degeneration. Using an ultrahigh field (7T) susceptibility-weighted imaging (SWI) sequence, it is possible to capture oxygen-level dependent contrast of submillimeter-sized vessels. Moreover, the quantitative susceptibility mapping (QSM) results derived from SWI data allow for the simultaneous estimation of venous oxygenation levels, thereby enhancing the understanding of hippocampal function. In this study, we proposed two potential imaging markers in a cohort of 19 healthy volunteers aged between 20 and 74 years. These markers were: 1) hippocampal venous density on SWI images and 2) venous susceptibility (Δχvein) in the hippocampus-associated draining veins (the inferior ventricular veins (IVV) and the basal veins of Rosenthal (BVR) using QSM images). They were chosen specifically to help characterize the oxygen utilization of the human hippocampus and medial temporal lobe (MTL). As part of the analysis, we demonstrated the feasibility of measuring hippocampal venous density and Δχvein in the IVV and BVR at 7T with high spatial resolution (0.25 × 0.25 × 1 mm3). Our results demonstrated the in vivo reconstruction of the hippocampal venous system, providing initial evidence regarding the presence of the venous arch structure within the hippocampus. Furthermore, we evaluated the age effect of the two quantitative estimates and observed a significant increase in Δχvein for the IVV with age (p=0.006, r2 = 0.369). This may suggest the potential application of Δχvein in IVV as a marker for assessing changes in atrophy-related hippocampal oxygen utilization in normal aging and neurodegenerative diseases such as AD and dementia.

Reduced Oxygen Extraction Fraction in Deep Cerebral Veins Associated with Cognitive Impairment in Multiple Sclerosis.

Studying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS). This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients. Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (SvO2) in the ICVs. Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of SvO2 (74.5 ± 1.89 % vs 72.4 ± 2.23 %) in patients with RRMS compared with age- and sex-matched healthy controls. Both the susceptibility of ICVs (r = 0.646, p = 0.004) and the SvO2 (r = -0.603, p = 0.008) exhibited a strong correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale. The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS.

Characterization of white matter lesions in multiple sclerosis using proton density and T1-relaxation measures.

PURPOSE: Although lesion dissemination in time is a defining characteristic of multiple sclerosis (MS), there is a limited understanding of lesion heterogeneity. Currently, conventional sequences such as fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W) data are used to assess MS lesions qualitatively. Estimating water content could provide a measure of local tissue rarefaction, or reduced tissue density, resulting from chronic inflammation. Our goal was to utilize the proton spin density (PD), derived from a rapid, multi-contrast STAGE (strategically acquired gradient echo) protocol to characterize white matter (WM) lesions seen on T2W, FLAIR and T1W data. MATERIALS AND METHODS: Twenty (20) subjects with relapsing-remitting MS were scanned at 3 T using T1W, T2-weighted, FLAIR and strategically acquired gradient echo (STAGE) sequences. PD and T1 maps were derived from the STAGE data. Disease severity scores, including Extended Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC), were correlated with total, high PD and high T1 lesion volumes. A probability map of high PD regions and all lesions across all subjects was generated. Five perilesional normal appearing WM (NAWM) bands surrounding the lesions were generated to compare the median PD and T1 values in each band with the lesional values and the global WM. RESULTS: T1W intensity was negatively correlated with PD as expected (R = -0.87, p < 0.01, R2 = 0.756) and the FLAIR signal was suppressed for high PD volumes within the lesions, roughly for PD ≥ 0.85. The threshold for high PD and T1 regions was set to 0.909 and 1953.6 ms, respectively. High PD regions showed a high probability of occurrence near the boundary of the lateral ventricles. EDSS score and nine-hole peg test (dominant and non-dominant hand) were significantly correlated with the total lesion volume and the volumes of high PD and T1 regions (p < 0.05). There was a significant difference in PD/T1 values between the high PD/T1 regions within the lesions and the remaining lesional tissue (p < 0.001). In addition, the PD values of the first NAWM perilesional band directly adjacent to the lesional boundary displayed a significant difference (p < 0.05) compared to the global WM. CONCLUSION: Lesions with high PD and T1s had the highest probability of occurrence at the boundary of the lateral ventricles and likely represent chronic lesions with significant local tissue rarefaction. Moreover, the perilesional NAWM exhibited subtly increasing PD and T1 values from the NAWM up to the lesion boundary. Unlike on the T1 maps, the perilesional band adjacent to the lesion boundary possessed a significantly higher PD value than the global WM PD values. This shows that PD maps were sensitive to the subtle changes in NAWM surrounding the lesions.

The iron burden of cerebral microbleeds contributes to brain atrophy through the mediating effect of white matter hyperintensity.

The goal of this work was to explore the total iron burden of cerebral microbleeds (CMBs) using a semi-automatic quantitative susceptibility mapping and to establish its effect on brain atrophy through the mediating effect of white matter hyperintensities (WMH). A total of 95 community-dwelling people were enrolled. Quantitative susceptibility mapping (QSM) combined with a dynamic programming algorithm (DPA) was used to measure the characteristics of 1309 CMBs. WMH were evaluated according to the Fazekas scale, and brain atrophy was assessed using a 2D linear measurement method. Histogram analysis was used to explore the distribution of CMBs susceptibility, volume, and total iron burden, while a correlation analysis was used to explore the relationship between volume and susceptibility. Stepwise regression analysis was used to analyze the risk factors for CMBs and their contribution to brain atrophy. Mediation analysis was used to explore the interrelationship between CMBs and brain atrophy. We found that the frequency distribution of susceptibility of the CMBs was Gaussian in nature with a mean of 201 ppb and a standard deviation of 84 ppb; however, the volume and total iron burden of CMBs were more Rician in nature. A weak but significant correlation between the susceptibility and volume of CMBs was found (r = -0.113, P < 0.001). The periventricular WMH (PVWMH) was a risk factor for the presence of CMBs (number: ß = 0.251, P = 0.014; volume: ß = 0.237, P = 0.042; total iron burden: ß = 0.238, P = 0.020) and was a risk factor for brain atrophy (third ventricle width: ß = 0.325, P = 0.001; Evans's index: ß = 0.323, P = 0.001). PVWMH had a significant mediating effect on the correlation between CMBs and brain atrophy. In conclusion, QSM along with the DPA can measure the total iron burden of CMBs. PVWMH might be a risk factor for CMBs and may mediate the effect of CMBs on brain atrophy.

Quantitative susceptibility mapping of both ring and non-ring white matter lesions in relapsing remitting multiple sclerosis.

BACKGROUND: Recent evidence suggests that the presence of magnetic susceptibility changes in MS lesions correlates with patients' expanded disability status scale (EDSS). PURPOSE: This study evaluated the presence of ring lesions (RLs) and non-RLs, as well as changes in lesion susceptibility and lesion volume over a two-year time period in relapsing-remitting multiple sclerosis (RRMS) patients and compared these measures to the EDSS. STUDY TYPE: Longitudinal cohort. MATERIALS AND METHODS: A total of forty-three (43) patients with RRMS were recruited for this study. All subjects underwent 3 T MRI at baseline and forty-one (41) subjects had follow-up scans over a two-year period. The protocol included T2 fluid attenuated inversion recovery (FLAIR), pre- and post-contrast 2D T1-weighted gradient echo imaging and susceptibility weighted imaging (SWI) sequences. All data were acquired prior to gadolinium-based contrast agent injection except for SWI and post-contrast T1-weighted data. Mean and peak susceptibilities of lesions were measured using quantitative susceptibility mapping (QSM). For the RLs, inner-/outer-diameters from SWI data and absolute intensity from the FLAIR data were measured. The susceptibility and volumes of RLs and non-RLs were correlated with EDSS. RESULTS: The number of RLs correlated positively with EDSS (p-value = 0.04), but the RL volumes did not show a correlation with EDSS. Measurements of the annular ring and regions with high susceptibility remained constant over time (p = 0.2). For non-ring QSM-positive (QSM+) lesions, the average susceptibility was significantly correlated to EDSS (p < 0.01.) This was also the case for lesion volume, as well as the product of volume and susceptibility when compared to EDSS (p < 0.01 for both). CONCLUSIONS: The susceptibility distribution and lesion volumes for the RLs remained almost constant over time, suggesting that the changes in pathophysiology of the RLs is a gradual process. On the other hand, the presence of more than one RL along with both volume and susceptibility of non-RL QSM+ lesions were significantly associated with increased disability as measured by EDSS. These findings may strengthen the role of QSM in assessing MS patients radiologically.

Vascular mapping of the human hippocampus using Ferumoxytol-enhanced MRI.

The hippocampus is a small but complex grey matter structure that plays an important role in spatial and episodic memory and can be affected by a wide range of pathologies including vascular abnormalities. In this work, we introduce the use of Ferumoxytol, an ultra-small superparamagnetic iron oxide (USPIO) agent, to induce susceptibility in the arteries (as well as increase the susceptibility in the veins) to map the hippocampal micro-vasculature and to evaluate the quantitative change in tissue fractional vascular density (FVD), in each of its subfields. A total of 39 healthy subjects (aged 35.4 ± 14.2 years, from 18 to 81 years old) were scanned with a high-resolution (0.22×0.44×1 mm3) dual-echo SWI sequence acquired at four time points during a gradual increase in Ferumoxytol dose (final dose = 4 mg/kg). The volumes of each subfield were obtained automatically from the pre-contrast T1-weighted data. The dynamically acquired SWI data were co-registered and adaptively combined to reduce the blooming artifacts from large vessels, preserving the contrast from smaller vessels. The resultant SWI data were used to segment the hippocampal vasculature and to measure the FVD ((volume occupied by vessels)/(total volume)) for each subfield. The hippocampal fissure, along with the fimbria, granular cell layer of the dentate gyrus and cornu ammonis layers (except for CA1), showed higher micro-vascular FVD than the other parts of hippocampus. The CA1 region exhibited a significant correlation with age (R = -0.37, p < 0.05). demonstrating an overall loss of hippocampal vascularity in the normal aging process. Moreover, the vascular density reduction was more prominent than the age correlation with the volume reduction (R = -0.1, p > 0.05) of the CA1 subfield, which would suggest that vascular degeneration may precede tissue atrophy.

Protocol-dependence of middle cerebral artery dilation to modest hypercapnia.

There is a need for improved understanding of how different cerebrovascular reactivity (CVR) protocols affect vascular cross-sectional area (CSA) to reduce error in CVR calculations when measures of vascular CSA are not feasible. In human participants, we delivered ∼±4 mm Hg end-tidal partial pressure of CO2 (PETCO2) relative to baseline through controlled delivery, and measured changes in middle cerebral artery (MCA) CSA (7 Tesla magnetic resonance imaging (MRI)), blood velocity (transcranial Doppler and Phase contrast MRI), and calculated CVR based on a 3-minute steady-state (+4 mm Hg PETCO2) and a ramp (-3 to +4 mm Hg of PETCO2). We observed that (1) the MCA did not dilate during the ramp protocol (slope for CSA across time P > 0.05; R2 = 0.006), but did dilate by ∼7% during steady-state hypercapnia (P < 0.05); and (2) MCA blood velocity CVR was not different between ramp and steady-state hypercapnia protocols (ramp: 3.8 ± 1.7 vs. steady-state: 4.0 ± 1.6 cm/s/mm Hg), although calculated MCA blood flow CVR was ∼40% greater during steady-state hypercapnia than during ramp (P < 0.05) with the discrepancy due to MCA CSA changes during steady-state hypercapnia. We propose that a ramp model, across a delta of -3 to +4 mm Hg PETCO2, may provide an alternative approach to collecting CVR measures in young adults with transcranial Doppler when CSA measures are not feasible. Novelty: We optimized a magnetic resonance imaging sequence to measure dynamic middle cerebral artery (MCA) cross-sectional area (CSA). A ramp model of hypercapnia elicited similar MCA blood velocity reactivity as the steady-state model while maintaining MCA CSA.

An Overview of Venous Abnormalities Related to the Development of Lesions in Multiple Sclerosis.

The etiology of multiple sclerosis (MS) is currently understood to be autoimmune. However, there is a long history and growing evidence for disrupted vasculature and flow within the disease pathology. A broad review of the literature related to vascular effects in MS revealed a suggestive role for abnormal flow in the medullary vein system. Evidence for venous involvement in multiple sclerosis dates back to the early pathological work by Charcot and Bourneville, in the mid-nineteenth century. Pioneering work by Adams in the 1980s demonstrated vasculitis within the walls of veins and venules proximal to active MS lesions. And more recently, magnetic resonance imaging (MRI) has been used to show manifestations of the central vein as a precursor to the development of new MS lesions, and high-resolution MRI using Ferumoxytol has been used to reveal the microvasculature that has previously only been demonstrated in cadaver brains. Both approaches may shed new light into the structural changes occurring in MS lesions. The material covered in this review shows that multiple pathophysiological events may occur sequentially, in parallel, or in a vicious circle which include: endothelial damage, venous collagenosis and fibrin deposition, loss of vessel compliance, venous hypertension, perfusion reduction followed by ischemia, medullary vein dilation and local vascular remodeling. We come to the conclusion that a potential source of MS lesions is due to locally disrupted flow which in turn leads to remodeling of the medullary veins followed by endothelial damage with the subsequent escape of glial cells, cytokines, etc. These ultimately lead to the cascade of inflammatory and demyelinating events which ensue in the course of the disease.

Imaging patients pre and post deep brain stimulation: Localization of the electrodes and their targets.

PURPOSE: Deep brain stimulation (DBS) has become a widely performed surgical procedure for patients with medically refractory movement disorders and mental disorders. It is clinically important to set up a MRI protocol to map the brain targets and electrodes of the patients before and after DBS and to understand the imaging artifacts caused by the electrodes. METHODS: Five patients with DBS electrodes implanted in the habenula (Hb), fourteen patients with globus pallidus internus (GPi) targeted DBS, three pre-DBS patients and seven healthy controls were included in the study. The MRI protocol consisted of magnetization prepared rapid acquisition gradient echo T1 (MPRAGE T1W), 3D multi-echo gradient recalled echo (ME-GRE) and 2D fast spin echo T2 (FSE T2W) sequences to map the brain targets and electrodes of the patients. Phantom experiments were also run to determine both the artifacts and the susceptibility of the electrodes. Signal to noise ratio (SNR) on T1W, T2W and GRE datasets were measured. The visibility of the brain structures was scored according to the Rose criterion. A detailed analysis of the characteristics of the electrodes in all three sequence types was performed to confirm the reliability of the postoperative MRI approach. In order to understand the signal behavior, we also simulated the corresponding magnitude data using the same imaging parameters as in the phantom sequences. RESULTS: The mean ± inter-subject variability of the SNRs, across the subjects for T1W, T2W, and GRE datasets were 20.1 ± 8.1, 14.9 ± 3.2, and 43.0 ± 7.6, respectively. High resolution MPRAGE T1W and FSE T2W data both showed excellent contrast for the habenula and were complementary to each other. The mean visibility of the habenula in the 25 cases for the MPRAGE T1W data was 5.28 ± 1.11; and the mean visibility in the 20 cases for the FSE T2W data was 5.78 ± 1.30. Quantitative susceptibility mapping (QSM), reconstructed from the ME-GRE sequence, provided sufficient contrast to distinguish the substructures of the globus pallidus. The susceptibilities of the GPi and globus pallidus externa (GPe) were 0.087 ± 0.013 ppm and 0.115 ± 0.015 ppm, respectively. FSE T2W sequences provided the best image quality with smallest image blooming of stimulator leads compared to MPRAGE T1W images and GRE sequence images, the measured diameters of electrodes were 1.91 ± 0.22, 2.77 ± 0.22, and 2.72 ± 0.20 mm, respectively. High resolution, high bandwidth and short TE (TE = 2.6 ms) GRE helped constrain the artifacts to the area of the electrodes and the dipole effect seen in the GRE filtered phase data provided an effective mean to locate the end of the DBS lead. CONCLUSION: The imaging protocol consisting of MPRAGE T1W, FSE T2W and ME-GRE sequences provided excellent pre- and post-operative visualization of the brain targets and electrodes for patients undergoing DBS treatment. Although the artifacts around the electrodes can be severe, sometimes these same artifacts can be useful in identifying their location.

Revealing vascular abnormalities and measuring small vessel density in multiple sclerosis lesions using USPIO.

BACKGROUND AND PURPOSE: Multiple Sclerosis (MS) is a progressive, inflammatory, neuro-degenerative disease of the central nervous system (CNS) characterized by a wide range of histopathological features including vascular abnormalities. In this study, an ultra-small superparamagnetic iron oxide (USPIO) contrast agent, Ferumoxytol, was administered to induce an increase in susceptibility for both arteries and veins to help better reveal the cerebral microvasculature. The purpose of this work was to examine the presence of vascular abnormalities and vascular density in MS lesions using high-resolution susceptibility weighted imaging (SWI). METHODS: Six subjects with relapsing remitting MS (RRMS, age = 47.3 ± 11.8 years with 3 females and 3 males) and fourteen age-matched healthy controls were scanned at 3 T with SWI acquired before and after the infusion of Ferumoxytol. Composite data was generated by registering the FLAIR data to the high resolution SWI data in order to highlight the vascular information in MS lesions. Both the central vein sign (CVS) and, a new measure, the multiple vessel sign (MVS) were identified, along with any vascular abnormalities, in the lesions on pre- and post-contrast SWI-FLAIR fusion data. The small vessel density within the periventricular normal-appearing white matter (NAWM) and the periventricular lesions were compared for all subjects. RESULTS: Averaged across two independent raters, a total of 530 lesions were identified across all patients. The total number of lesions with vascularity on pre- and post-contrast data were 287 and 488, respectively. The lesions with abnormal vascular behavior were broken up into following categories: small lesions appearing only at the vessel boundary; dilated vessels within the lesions; and developmental venous angiomas. These vessel abnormalities observed within lesions increased from 55 on pre-contrast data to 153 on post-contrast data. Finally, across all the patients, the periventricular lesional vessel density was significantly higher (p < 0.05) than that of the periventricular NAWM. CONCLUSIONS: By inducing a super-paramagnetic susceptibility in the blood using Ferumoxytol, the vascular abnormalities in the RRMS patients were revealed and small vessel densities were obtained. This approach has the potential to monitor the venous vasculature present in MS lesions, catalogue their characteristics and compare the vascular structures spatially to the presence of lesions. These enhanced vascular features may provide new insight into the pathophysiology of MS.

VC-Net: Deep Volume-Composition Networks for Segmentation and Visualization of Highly Sparse and Noisy Image Data.

The fundamental motivation of the proposed work is to present a new visualization-guided computing paradigm to combine direct 3D volume processing and volume rendered clues for effective 3D exploration. For example, extracting and visualizing microstructures in-vivo have been a long-standing challenging problem. However, due to the high sparseness and noisiness in cerebrovasculature data as well as highly complex geometry and topology variations of micro vessels, it is still extremely challenging to extract the complete 3D vessel structure and visualize it in 3D with high fidelity. In this paper, we present an end-to-end deep learning method, VC-Net, for robust extraction of 3D microvascular structure through embedding the image composition, generated by maximum intensity projection (MIP), into the 3D volumetric image learning process to enhance the overall performance. The core novelty is to automatically leverage the volume visualization technique (e.g., MIP - a volume rendering scheme for 3D volume images) to enhance the 3D data exploration at the deep learning level. The MIP embedding features can enhance the local vessel signal (through canceling out the noise) and adapt to the geometric variability and scalability of vessels, which is of great importance in microvascular tracking. A multi-stream convolutional neural network (CNN) framework is proposed to effectively learn the 3D volume and 2D MIP feature vectors, respectively, and then explore their inter-dependencies in a joint volume-composition embedding space by unprojecting the 2D feature vectors into the 3D volume embedding space. It is noted that the proposed framework can better capture the small/micro vessels and improve the vessel connectivity. To our knowledge, this is the first time that a deep learning framework is proposed to construct a joint convolutional embedding space, where the computed vessel probabilities from volume rendering based 2D projection and 3D volume can be explored and integrated synergistically. Experimental results are evaluated and compared with the traditional 3D vessel segmentation methods and the state-of-the-art in deep learning, by using extensive public and real patient (micro- )cerebrovascular image datasets. The application of this accurate segmentation and visualization of sparse and complicated 3D microvascular structure facilitated by our method demonstrates the potential in a powerful MR arteriogram and venogram diagnosis of vascular disease.

Multi-Echo Quantitative Susceptibility Mapping for Strategically Acquired Gradient Echo (STAGE) Imaging.

PURPOSE: To develop a method to reconstruct quantitative susceptibility mapping (QSM) from multi-echo, multi-flip angle data collected using strategically acquired gradient echo (STAGE) imaging. METHODS: The 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. RESULTS: The 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. CONCLUSION: This 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.

Subvoxel vascular imaging of the midbrain using USPIO-Enhanced MRI.

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 â€‹× â€‹0.44 â€‹× â€‹1 â€‹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 â€‹= â€‹4 â€‹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 â€‹µm-100 â€‹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 â€‹µm should be visible with the maximum dose of 4 â€‹mg/kg.

Quantitative Susceptibility Mapping for Characterization of Intraplaque Hemorrhage and Calcification in Carotid Atherosclerotic Disease.

BACKGROUND: Carotid artery intraplaque hemorrhage (IPH), an unstable component of atherosclerosis, is associated with an increased risk of stroke. PURPOSE: To investigate quantitative susceptibility mapping (QSM) as a tool for the evaluation of IPH and calcification in vivo. STUDY TYPE: Prospective. POPULATION: Ten healthy volunteers and 15 patients. FIELD STRENGTH/SEQUENCE: 3.0T Susceptibility-weighted imaging (SWI), magnetization-prepared rapid acquisition with gradient echo (MP-RAGE), T1 -weighted sampling perfection with application of optimized contrasts using different flip angle evolution (T1 -SPACE), T2 -weighted turbo spin-echo (T2 WI), and time-of-flight (TOF) sequences. ASSESSMENT: The vessel wall area of the carotid artery was measured with QSM and compared with T1 -SPACE on healthy volunteers. Four radiologists, blinded to clinical history and patient identity, determined the presence and area of IPH on MP-RAGE and QSM, as well as the area of calcification on T1 -SPACE and QSM. STATISTICAL TESTS: Bland-Altman analysis, Pearson correlation coefficients, linear regression analyses were performed to evaluate the concordance of area measurements. Cohen's kappa (κ) was analyzed to determine the agreement between IPH detections. The paired t-test was used to compare the group differences. RESULTS: In 423 matched slices, 20.1% (85/423) and 19.6% (83/423) were detected to have IPH on MP-RAGE and QSM, respectively. IPH detection by QSM and MP-RAGE showed good agreement (κ = 0.822, P < 0.001) between the two methods. There was no significant difference in IPH area measurements between QSM and MP-RAGE (7.28 mm2 ± 6.41 vs. 7.16 mm2 ± 5.99, P = 0.575). There was no significant difference in calcification area measurement between QSM and T1 -SPACE (3.51 mm2 ± 1.78 vs. 3.41 mm2 ± 2.02, P = 0.783). DATA CONCLUSION: QSM is a novel imaging tool for the identification of IPH in patients with carotid atherosclerosis and enables differentiation of IPH and calcification. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1 J. Magn. Reson. Imaging 2020;52:534-541.

Detecting sub-voxel microvasculature with USPIO-enhanced susceptibility-weighted MRI at 7 T.

BACKGROUND: Susceptibility weighted imaging (SWI) combines phase with magnitude information to better image sub-voxel veins. Recently, it has been extended to image very small sub-voxel arteries and veins by injecting intravenously the ultra-small superparamagnetic iron oxide, Ferumoxytol. OBJECTIVE: To determine practical experimental imaging parameters for sub-voxel cerebral vessels at 7 T. METHODS: Six Wistar-Kyoto rats aged 7-13 weeks were imaged. For a given spatial resolution, SWI was acquired pre- and post- Ferumoxytol with doses of 2, 4, 6 and 8 mg/kg and echo times (TEs) of 5, 10 and 15 ms at each dose. The spatial resolutions of 62.5 × 125 × 250 µm3 (acquisition time of 7.5 min) and 62.5 × 62.5 × 125 µm3 (30 min) were used. Both SWI and quantitative susceptibility mapping (QSM) data were analyzed. Contrast-to-noise ratio (CNR) was measured and used to determine the optimal practical imaging parameters for detection of small cortical penetrating arteries. RESULTS: For a given spatial resolution with an aspect ratio (frequency: phase: slice) of 2:4:8 relative to the vessel size, we found the TE-dose index (TE x dose) must be at least 40 ms·mg/kg for both SWI and QSM to reveal the most vessels. The higher the TE-dose index, the better the image quality for both SWI and QSM up to 60 ms·mg/kg. CONCLUSIONS: There is an optimal TE-dose index for improved visualization of sub-voxel vessels. Choosing the smallest TE and the largest allowed dose made it possible to run the sequence efficiently. In practice, the aspect ratio of 2:4:8 and the TE-dose index ranging from 40 to 60 ms·mg/kg provided the optimal and most practical solution.

Dual-Imaging Modality Approach to Evaluate Cerebral Hemodynamics in Growth-Restricted Fetuses: Oxygenation and Perfusion.

OBJECTIVE: To evaluate a dual-imaging modality approach to obtain a combined estimation of venous blood oxygenation (SνO2) using susceptibility-weighted magnetic resonance imaging (SWI-MRI), and blood perfusion using power Dopp-ler ultrasound (PDU) and fractional moving blood volume (FMBV) in the brain of normal growth and growth-restricted fetuses. METHODS: Normal growth (n = 33) and growth-restricted fetuses (n = 10) from singleton pregnancies between 20 and 40 weeks of gestation were evaluated. MRI was performed and SνO2 was calculated using SWI-MRI data obtained in the straight section of the superior sagittal sinus. Blood perfusion was estimated using PDU and FMBV from the frontal lobe in a mid-sagittal plane of the fetal brain. The association between fetal brain SνO2 and FMBV, and the distribution of SνO2 and FMBV values across gestation were calculated for both groups. RESULTS: In growth-restricted fetuses, the brain SνO2 values were similar, and the FMBV values were higher across gestation as compared to normal growth fetuses. There was a significantly positive association between SνO2 and FMBV values (slope = 0.38 ± 0.12; r = 0.7; p = 0.02) in growth-restricted fetuses. In normal growth fetuses, SνO2 showed a mild decreasing trend (slope = -0.7 ± 0.4; p = 0.1), whereas FMBV showed a mild increasing trend (slope = 0.2 ± 0.2; p = 0.2) with advancing gestation, and a mild but significant negative association (slope = -0.78 ± 0.3; r = -0.4; p = 0.04) between these two estimates. CONCLUSION: Combined MRI (SWI) and ultrasound (FMBV) techniques showed a significant association between cerebral blood oxygenation and blood perfusion in normal growth and growth-restricted fetuses. This dual-imaging approach could contribute to the early detection of fetal "brain sparing" and brain oxygen saturation changes in high-risk pregnancies.

Using variable-rate selective excitation (VERSE) radiofrequency pulses to reduce power deposition in pulsed arterial spin labeling sequence at 7 Tesla.

PURPOSE: Arterial spin labeling (ASL) is an established noninvasive MRI technique used for cerebral blood flow measurement, which generally suffers from a low signal-to-noise ratio (SNR). The use of ultra-high fields to enhance sensitivity inevitably results in an increase in TR because of specific absorption rate (SAR) constraints, causing inadequate sampling of hemodynamic response in functional MRI, and adversely affecting concurrent measurement such as blood oxygen level dependent. To address this problem, variable-rate selective excitation (VERSE) radiofrequency (RF) pulses were used. METHODS: The conventional (sinc) selective RF pulses of the Q2TIPS block in the PICORE pulsed ASL (PASL) sequence used for blood saturation were replaced by their equivalent VERSE RF waveforms. Nine healthy volunteers were scanned using the conventional and VERSE PASL sequences on a head-only 7T scanner operating in parallel transmit mode. RESULTS: VERSE PASL sequence provides perfusion images similar to the conventional version, with comparable perfusion SNR (conventional, 3.33 ± 0.48; VERSE, 3.26 ± 0.55) and temporal SNR (conventional, 1.02 ± 0.20; VERSE, 1.05 ± 0.12) for TR = 3.5 seconds and 70 measurements. With shorter acquisition time (TR = 2.5 seconds), VERSE PASL sequence still provides similar results to those acquired using the conventional PASL sequence with longer TR = 3.5 seconds. CONCLUSION: The use of VERSE RF pulses in the Q2TIPS block of a PASL sequence allowed for the reduction of RF power deposition and, consequently, an increase in the temporal resolution and/or perfusion SNR.