•Quantitative susceptibility mapping (QSM) provides tissue composition information.•Iron contributes to neurodegeneration and is a main driver of QSM signal.•PET reflects protein aggregation and ...cellular changes in neurodegenerative disease.•Associations of QSM and PET may reflect role of iron in neurodegeneration.•Iron deposition with neuroinflammation contributes to these associations.
Quantitative susceptibility mapping (QSM) has been used to study susceptibility changes that may occur based on tissue composition and mineral deposition. Iron is a primary contributor to changes in magnetic susceptibility and of particular interest in applications of QSM to neurodegeneration and aging. Iron can contribute to neurodegeneration through inflammatory processes and via interaction with aggregation of disease-related proteins. To better understand the local susceptibility changes observed on QSM, its signal has been studied in association with other imaging metrics such as positron emission tomography (PET). The associations of QSM and PET may provide insight into the pathophysiology of disease processes, such as the role of iron in aging and neurodegeneration, and help to determine the diagnostic utility of QSM as an indirect indicator of disease processes typically evaluated with PET. In this review we discuss the proposed mechanisms and summarize prior studies of the associations of QSM and amyloid PET, tau PET, TSPO PET, FDG-PET, 15O-PET, and F-DOPA PET in evaluation of neurologic diseases with a focus on aging and neurodegeneration.
Alzheimer's disease (AD) is the leading cause of cognitive impairment and dementia worldwide with rising prevalence, incidence and mortality. Despite many decades of research, there remains an unmet ...need for disease‐modifying treatment that can significantly alter the progression of disease. Recently, with United States Food and Drug Administration (FDA) drug approvals, there have been tremendous advances in this area, with agents demonstrating effects on cognition and biomarkers. Magnetic resonance imaging (MRI) plays an instrumental role in these trials. This review article aims to outline how MRI is used for screening eligibility, monitoring safety and measuring efficacy in clinical trials, leaning on the landscape of past and recent AD clinical trials that have used MRI as examples; further, insight on promising MRI biomarkers for future trials is provided. Level of Evidence 1. Technical Efficacy Stage 4.
Altered iron metabolism has been hypothesized to be associated with Alzheimer's disease pathology, and prior work has shown associations between iron load and beta amyloid plaques. Quantitative ...susceptibility mapping (QSM) is a recently popularized MR technique to infer local tissue susceptibility secondary to the presence of iron as well as other minerals. Greater QSM values imply greater iron concentration in tissue. QSM has been used to study relationships between cerebral iron load and established markers of Alzheimer's disease, however relationships remain unclear. In this work we study QSM signal characteristics and associations between susceptibility measured on QSM and established clinical and imaging markers of Alzheimer's disease. The study included 421 participants (234 male, median age 70 years, range 34–97 years) from the Mayo Clinic Study of Aging and Alzheimer's Disease Research Center; 296 (70%) had a diagnosis of cognitively unimpaired, 69 (16%) mild cognitive impairment, and 56 (13%) amnestic dementia. All participants had multi-echo gradient recalled echo imaging, PiB amyloid PET, and Tauvid tau PET. Variance components analysis showed that variation in cortical susceptibility across participants was low. Linear regression models were fit to assess associations with regional susceptibility. Expected increases in susceptibility were found with older age and cognitive impairment in the deep and inferior gray nuclei (pallidum, putamen, substantia nigra, subthalamic nucleus) (betas: 0.0017 to 0.0053 ppm for a 10 year increase in age, p = 0.03 to <0.001; betas: 0.0021 to 0.0058 ppm for a 5 point decrease in Short Test of Mental Status, p = 0.003 to p<0.001). Effect sizes in cortical regions were smaller, and the age associations were generally negative. Higher susceptibility was significantly associated with higher amyloid PET SUVR in the pallidum and putamen (betas: 0.0029 and 0.0012 ppm for a 20% increase in amyloid PET, p = 0.05 and 0.02, respectively), higher tau PET in the basal ganglia with the largest effect size in the pallidum (0.0082 ppm for a 20% increase in tau PET, p<0.001), and with lower cortical gray matter volume in the medial temporal lobe (0.0006 ppm for a 20% decrease in volume, p = 0.03). Overall, these findings suggest that susceptibility in the deep and inferior gray nuclei, particularly the pallidum and putamen, may be a marker of cognitive decline, amyloid deposition, and off-target binding of the tau ligand. Although iron has been demonstrated in amyloid plaques and in association with neurodegeneration, it is of insufficient quantity to be reliably detected in the cortex using this implementation of QSM.
•Pathological alteration in AD is investigated using separated diamagnetic maps from DECOMPOSE-QSM.•Absolute diamagnetic susceptibility in AD GM is affected by protein aggregation and ...demyelination.•AD WM show lower absolute diamagnetic susceptibility compared to controls due to demyelination.•Decreased β-amyloid protein in CSF may lessen absolute diamagnetic susceptibility in AD.
A sensitive and accurate imaging technique capable of tracking the disease progression of Alzheimer's Disease (AD) driven amnestic dementia would be beneficial. A currently available method for pathology detection in AD with high accuracy is Positron Emission Tomography (PET) imaging, despite certain limitations such as low spatial resolution, off-targeting error, and radiation exposure. Non-invasive MRI scanning with quantitative magnetic susceptibility measurements can be used as a complementary tool. To date, quantitative susceptibility mapping (QSM) has widely been used in tracking deep gray matter iron accumulation in AD. The present work proposes that by compartmentalizing quantitative susceptibility into paramagnetic and diamagnetic components, more holistic information about AD pathogenesis can be acquired. Particularly, diamagnetic component susceptibility (DCS) can be a powerful indicator for tracking protein accumulation in the gray matter (GM), demyelination in the white matter (WM), and relevant changes in the cerebrospinal fluid (CSF). In the current work, voxel-wise group analysis of the WM and the CSF regions show significantly lower |DCS| (the absolute value of DCS) value for amnestic dementia patients compared to healthy controls. Additionally, |DCS| and τ PET standardized uptake value ratio (SUVr) were found to be associated in several GM regions typically affected by τ deposition in AD. Therefore, we propose that the separated diamagnetic susceptibility can be used to track pathological neurodegeneration in different tissue types and regions of the brain. With the initial evidence, we believe the usage of compartmentalized susceptibility demonstrates substantive potential as an MRI-based technique for tracking AD-driven neurodegeneration.
The etiology of sporadic cavernous malformations is not well-understood. However, recent evidence suggests that they may arise from a developmental venous anomaly. The goal of this study was to ...evaluate the prevalence of developmental venous anomalies associated with sporadic cavernous malformations using 7T MR imaging.
We retrospectively identified patients with a sporadic cavernous malformation imaged with 7T MR imaging between August 2019 and July 2022. Two raters determined whether a developmental venous anomaly was associated with each malformation.
The study included 59 patients with a total of 61 cavernous malformations. Of the sixty-one, 44 (72%) had an associated developmental venous anomaly. An associated anomaly was most common for cavernous malformations in the brainstem (88%) compared with the cerebral hemispheres or cerebellum (60%-67%).
By means of high-quality 7T imaging, most patients with a sporadic cavernous malformation were found to have an associated developmental venous anomaly. These findings support the hypothesis that cavernous malformations may arise secondary to hemodynamic abnormalities.
...they argue that our assumption of constant variation in QSM across regions may bias the variance estimates for selected regions; our Figure 1 does indeed suggest that residual variation differs ...across the deep and inferior gray regions. ...the primary goal of our manuscript was to assess the relationship between susceptibility in deep and inferior gray and cortical regions with clinical and imaging biomarkers. The last sentence of Cogswell et al. still provides a useful and succinct summary which is unchanged regardless of the variance analysis: “Overall, our findings suggest that QSM may be an informative marker in the deep and inferior gray nuclei but in the current implementation has a limited role in the cortex for clinical evaluation along the aging to dementia spectrum.”
•3D T1-w, 3D T2-w, and 3D T2-FLAIR were all highly re-identifiable (96–98%).•2D T2-FLAIR and 3D multi-echo GRE were each moderately re-identifiable (44–45%).•Diffusion, functional and ASL were each ...minimally re-identifiable (0–8%).•mri_reface reduced all re-identification rates to ≤8%.•mri_reface effects on brain measurements were all below or similar to scan-rescan.
It is now widely known that research brain MRI, CT, and PET images may potentially be re-identified using face recognition, and this potential can be reduced by applying face-deidentification (“de-facing”) software. However, for research MRI sequences beyond T1-weighted (T1-w) and T2-FLAIR structural images, the potential for re-identification and quantitative effects of de-facing are both unknown, and the effects of de-facing T2-FLAIR are also unknown. In this work we examine these questions (where applicable) for T1-w, T2-w, T2*-w, T2-FLAIR, diffusion MRI (dMRI), functional MRI (fMRI), and arterial spin labelling (ASL) sequences. Among current-generation, vendor-product research-grade sequences, we found that 3D T1-w, T2-w, and T2-FLAIR were highly re-identifiable (96–98%). 2D T2-FLAIR and 3D multi-echo GRE (ME-GRE) were also moderately re-identifiable (44–45%), and our derived T2* from ME-GRE (comparable to a typical 2D T2*) matched at only 10%. Finally, diffusion, functional and ASL images were each minimally re-identifiable (0–8%). Applying de-facing with mri_reface version 0.3 reduced successful re-identification to ≤8%, while differential effects on popular quantitative pipelines for cortical volumes and thickness, white matter hyperintensities (WMH), and quantitative susceptibility mapping (QSM) measurements were all either comparable with or smaller than scan-rescan estimates. Consequently, high-quality de-facing software can greatly reduce the risk of re-identification for identifiable MRI sequences with only negligible effects on automated intracranial measurements. The current-generation echo-planar and spiral sequences (dMRI, fMRI, and ASL) each had minimal match rates, suggesting that they have a low risk of re-identification and can be shared without de-facing, but this conclusion should be re-evaluated if they are acquired without fat suppression, with a full-face scan coverage, or if newer developments reduce the current levels of artifacts and distortion around the face.
Numerous recent technological advances offer the potential to substantially enhance the MRI evaluation of moyamoya disease (MMD). These include high-resolution volumetric imaging, high-resolution ...vessel wall characterization, improved cerebral angiographic and perfusion techniques, high-field imaging, fast scanning methods, and artificial intelligence. This review discusses the current state-of-the-art MRI applications in these realms, emphasizing key imaging findings, clinical utility, and areas that will benefit from further investigation. Although these techniques may apply to imaging of a wide array of neurovascular or other neurological conditions, consideration of their application to MMD is useful given the comprehensive multidimensional MRI assessment used to evaluate MMD. These MRI techniques span from basic cross-sectional to advanced functional sequences, both qualitative and quantitative.The aim of this review was to provide a comprehensive summary and analysis of current key relevant literature of advanced MRI techniques for the evaluation of MMD with image-rich case examples. These imaging methods can aid clinical characterization, help direct treatment, assist in the evaluation of treatment response, and potentially improve the understanding of the pathophysiology of MMD.
Whether a relationship exists between cerebrovascular disease and Alzheimer's disease has been a source of controversy. Evaluation of the temporal progression of imaging biomarkers of these disease ...processes may inform mechanistic associations. We investigate the relationship of disease trajectories of cerebrovascular disease (white matter hyperintensity, WMH, and fractional anisotropy, FA) and Alzheimer's disease (amyloid and tau PET) biomarkers in 2406 Mayo Clinic Study of Aging and Mayo Alzheimer's Disease Research Center participants using accelerated failure time models. The model assumes a common pattern of progression for each biomarker that is shifted earlier or later in time for each individual and represented by a per participant age adjustment. An individual's amyloid and tau PET adjustments show very weak temporal association with WMH and FA adjustments (R = -0.07 to 0.07); early/late amyloid or tau timing explains <1% of the variation in WMH and FA adjustment. Earlier onset of amyloid is associated with earlier onset of tau (R = 0.57, R
= 32%). These findings support a strong mechanistic relationship between amyloid and tau aggregation, but not between WMH or FA and amyloid or tau PET.
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