Inversion Recovery Magnetic Resonance Imaging Research Articles

Comparing the Saccule-to-Utricle Ratio in Early- Versus Late-Stage Meniere's Disease Patients.

To compare the saccule-to-utricle ratio in early- versus late-stage Meniere's disease (MD) patients based on magnetic resonance imaging (MRI) images. In this retrospective study, we performed 3-dimensional real inversion recovery (3D-real IR) MRI 24 h after intratympanic gadolinium administration in unilateral MD patients at early-stage (n = 56) and late-stage (n = 70). Two radiologists independently graded endolymphatic hydrops (EH) and the saccule-to-utricle ratio inversion (SURI) was compared between the two groups. Furthermore, early-stage MD patients were further divided into two subgroups based on disease duration: ≤6 months (n = 20) and >6 months (n = 36) and the SURI was compared. Among the 56 patients in the early-stage group, 26 cases (46.43%) exhibited an enlarged saccule that is larger than the utricle, showing SURI. In contrast, among the late-stage MD, only four cases (5.71%) showed SURI (p < 0.001). In the early-stage MD subgroup with a disease duration of ≤6 months, the proportion of SURI was 70% (14/20), which was higher than that in the subgroup with a disease duration of >6 months (33.33%, 12/36, p = 0.02). SURI may serve as an effective imaging marker for diagnosis of early-stage MD. Our finding suggests that endolymphatic hydrops in MD may primarily originate from the saccule. 3 Laryngoscope, 134:5116-5121, 2024.

Positive Predictive Value of Contrast-Enhanced Fluid-Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging in Diagnosis of Meningitis Among Pediatrics Taking Cerebrospinal Fluid Analysis as Gold Standard

Positive Predictive Value of Contrast-Enhanced Fluid-Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging in Diagnosis of Meningitis Among Pediatrics Taking Cerebrospinal Fluid Analysis as Gold Standard

Prediction of early recurrence of adult-type diffuse gliomas following radiotherapy using multi-modal magnetic resonance images.

Adult-type diffuse gliomas are among the central nervous system's most aggressive malignant primary neoplasms. Despite advancements in systemic therapies and technological improvements in radiation oncology treatment delivery, the survival outcome for these patients remains poor. Fast and accurate assessment of tumor response to oncologic treatments is crucial, as it can enable the early detection of recurrent or refractory gliomas, thereby allowing timely intervention with life-prolonging salvage therapies. Radiomics is a developing field with great potential to improve medical image interpretation. This study aims to apply a radiomics-based predictive model for classifying response to radiotherapy within the first 3 months post-treatment. Ninety-five patients were selected from the Burdenko Glioblastoma Progression Dataset. Tumor regions were delineated in the axial plane on contrast-enhanced T1(CE T1W) and T2 fluid-attenuated inversion recovery (T2_FLAIR) magnetic resonance imaging (MRI). Hand-crafted radiomic (HCR) features, including first- and second-order features, were extracted using PyRadiomics (3.7.6) in Python (3.10). Then, recursive feature elimination with a random forest (RF) classifier was applied for feature dimensionality reduction. RF and support vector machine (SVM) classifiers were built to predict treatment outcomes using the selected features. Leave-one-out cross-validation was employed to tune hyperparameters and evaluate the models. For each segmented target, 186 HCR features were extracted from the MRI sequence. Using the top-ranked radiomic features from a combination of CE T1W and T2_FLAIR, an optimized classifier achieved the highest averaged area under the curve (AUC) of 0.829±0.075 using the RF classifier. The HCR features of CE T1W produced the worst outcomes among all models (0.603±0.024 and 0.615±0.075 for RF and SVM classifiers, respectively). We developed and evaluated a radiomics-based predictive model for early tumor response to radiotherapy, demonstrating excellent performance supported by high AUC values. This model, harnessing radiomic features from multi-modal MRI, showed superior predictive performance compared to single-modal MRI approaches. These results underscore the potential of radiomics in clinical decision support for this disease process.

Oxygen Extraction Fraction Mapping on Admission Magnetic Resonance Imaging May Predict Recovery of Hyperacute Ischemic Brain Lesions After Successful Thrombectomy: A Retrospective Observational Study.

In acute stroke, diffusion-weighted imaging (DWI) is used to assess the ischemic core. Dynamic-susceptibility contrast perfusion magnetic resonance imaging allows an estimation of the oxygen extraction fraction (OEF), but the outcome of DWI lesions with increased OEF postrecanalization is unclear. This study investigated the impact of OEF on the fate of DWI lesions in patients achieving recanalization after thrombectomy. This was a retrospective analysis of the HIBISCUS-STROKE cohort (Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke; NCT: 03149705), a single-center observational study that prospectively enrolled patients who underwent magnetic resonance imaging triage for thrombectomy and a day-6 T2-fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging. Automated postprocessing of admission dynamic-susceptibility contrast perfusion magnetic resonance imaging generated OEF maps. At visual analysis, the OEF status within DWI lesions was assessed in comparison to the contralateral side and correlated with volume changes (difference of ischemic lesion between admission DWI and registered day-6 T2-FLAIR). At voxel-based analysis, recovered DWI regions (lesions present on the admission DWI but absent on the registered day-6 T2-FLAIR) and nonrecovered regions were segmented to extract semiquantitative OEF values. Of the participants enrolled from 2016 to 2022, 134 of 321 (41.7%) were included (median age, 71.0 years; 58.2% male; median baseline National Institutes of Health Scale score, 15.0). At visual analysis, 46 of 134 (34.3%) patients had increased OEF within DWI lesions. These patients were more likely to show a reduction in ischemic lesion volumes compared with those without increased OEF (median change, -4.0 versus 4.8 mL; P<0.0001). Multivariable analysis indicated that increased OEF within DWI lesions was associated with a reduction in ischemic lesion volumes from admission DWI to day-6 T2-FLAIR (odds ratio, 0.68 [95% CI, 0.49-0.87]; P=0.008). At voxel-based analysis, recovered DWI regions had increased OEF, while nonrecovered regions had decreased OEF (median, 126.9% versus -27.0%; P<0.0001). Increased OEF within hyperacute DWI lesions was associated with ischemic lesion recovery between admission DWI and day-6 T2-FLAIR in patients achieving recanalization after thrombectomy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03149705.

Coma Due to Artery of Percheron Infarction: An Unusual Case Report

Ischemic stroke attributable to obstruction of the artery of Percheron (AOP), an infrequent anatomical arterial variant perfusing both medial thalami, can pose difficult diagnostic challenges. Obstruction or occlusion of the AOP results in bilateral paramedian thalamic infarction which is an unusual and rare vascular cause of coma. We present a 65-year-old male patient who came to the emergency department with altered sensorium for 10 days. The initial computed tomography (CT) brain was normal, followed by subsequent CT revealing an ill-defined hypodensity in the ventromedial aspect of the left thalamus and ventral aspect of the midbrain. T2/fluid-attenuated inversion recovery magnetic resonance imaging illustrated hyperintensity in the mesencephalon and bilateral paramedian thalami with restricted diffusion, suggesting an AOP infarct.

Characterization of white matter hyperintensities in Down syndrome.

In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored. In 261 DS adults and 131 euploid controls, fluid-attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume. In DS, total WMHs arose at age 43 and showed stronger associations with age than in controls. WMH volume increased along the AD continuum, particularly in periventricular regions, and frontal, parietal, and occipital lobes. Associations were found with CSF biomarkers and temporo-parietal GM volumes. WMHs increase 10 years before AD symptom onset in DS and are closely linked with AD biomarkers and neurodegeneration. This suggests a direct connection to AD pathophysiology, independent of vascular risks. White matter hyperintensities (WMHs) increased 10 years before Alzheimer's disease symptom onset in Down syndrome (DS). WMHs were strongly associated in DS with the neurofilament light chain biomarker. WMHs were more associated in DS with gray matter volume in parieto-temporal areas.

Central Vein Sign and Paramagnetic Rim Lesions: Susceptibility Changes in Brain Tissues and Their Implications for the Study of Multiple Sclerosis Pathology.

Multiple sclerosis (MS) is the most common acquired inflammatory and demyelinating disease in adults. The conventional diagnostic of MS and the follow-up of inflammatory activity is based on the detection of hyperintense foci in T2 and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and lesions with brain-blood barrier (BBB) disruption in the central nervous system (CNS) parenchyma. However, T2/FLAIR hyperintense lesions are not specific to MS and the MS pathology and inflammatory processes go far beyond focal lesions and can be independent of BBB disruption. MRI techniques based on the magnetic susceptibility properties of the tissue, such as T2*, susceptibility-weighted images (SWI), and quantitative susceptibility mapping (QSM) offer tools for advanced MS diagnostic, follow-up, and the assessment of more detailed features of MS dynamic pathology. Susceptibility-weighted techniques are sensitive to the paramagnetic components of biological tissues, such as deoxyhemoglobin. This capability enables the visualization of brain parenchymal veins. Consequently, it presents an opportunity to identify veins within the core of multiple sclerosis (MS) lesions, thereby affirming their venocentric characteristics. This advancement significantly enhances the accuracy of the differential diagnostic process. Another important paramagnetic component in biological tissues is iron. In MS, the dynamic trafficking of iron between different cells, such as oligodendrocytes, astrocytes, and microglia, enables the study of different stages of demyelination and remyelination. Furthermore, the accumulation of iron in activated microglia serves as an indicator of latent inflammatory activity in chronic MS lesions, termed paramagnetic rim lesions (PRLs). PRLs have been correlated with disease progression and degenerative processes, underscoring their significance in MS pathology. This review will elucidate the underlying physical principles of magnetic susceptibility and their implications for the formation and interpretation of T2*, SWI, and QSM sequences. Additionally, it will explore their applications in multiple sclerosis (MS), particularly in detecting the central vein sign (CVS) and PRLs, and assessing iron metabolism. Furthermore, the review will discuss their role in advancing early and precise MS diagnosis and prognostic evaluation, as well as their utility in studying chronic active inflammation and degenerative processes.

Association of audiovestibular findings with fluid-attenuated inversion recovery magnetic resonance imaging in patients with vestibular schwannoma

BackgroundVestibular schwannoma (VS) is a benign tumor of the vestibular nerve. Flair-attenuated inversion recovery (FLAIR) of magnetic resonance imaging (MRI) images are sensitive in detecting high protein contents of fluids. ObjectivesTo investigate the association between signal intensity (SI) on FLAIR images and audiovestibular findings in patients with VS. MethodsMedical records of twenty-five patients with VS were retrospectively analyzed. ResultsLarger tumors were associated with increased FLAIR SI of the cochlea, vestibule, and semicircular canal (SCC) on the affected side compared to those of the unaffected side. Pure-tone audiometry (PTA), and speech audiometry were associated with the SI of the affected cochlea. There was no significant correlation between the SI of the vestibule and vestibular evoked myogenic potential, SI of the SCC, and caloric test or video head impulse test results. ConclusionOur study suggests that tumor size was significantly associated with high SI on FLAIR imaging, and audiological findings were associated with the SI of the affected cochlea. Further studies with larger cohorts are required to confirm the association between vestibular function and FLAIR imaging in VS.

A non-invasive AI-based system for precise grading of anosmia in COVID-19 using neuroimaging

COVID-19 (Coronavirus), an acute respiratory disorder, is caused by SARS-CoV-2 (coronavirus severe acute respiratory syndrome). The high prevalence of COVID-19 infection has drawn attention to a frequent illness symptom: olfactory and gustatory dysfunction. The primary purpose of this manuscript is to create a Computer-Assisted Diagnostic (CAD) system to determine whether a COVID-19 patient has normal, mild, or severe anosmia. To achieve this goal, we used fluid-attenuated inversion recovery (FLAIR) Magnetic Resonance Imaging (FLAIR-MRI) and Diffusion Tensor Imaging (DTI) to extract the appearance, morphological, and diffusivity markers from the olfactory nerve. The proposed system begins with the identification of the olfactory nerve, which is performed by a skilled expert or radiologist. It then proceeds to carry out the subsequent primary steps: (i) extract appearance markers (i.e., 1st and 2nd order markers), morphology/shape markers (i.e., spherical harmonics), and diffusivity markers (i.e., Fractional Anisotropy (FA) & Mean Diffusivity (MD)), (ii) apply markers fusion based on the integrated markers, and (iii) determine the decision and corresponding performance metrics based on the most-promising classifier. The current study is unusual in that it ensemble bags the learned and fine-tuned ML classifiers and diagnoses olfactory bulb (OB) anosmia using majority voting. In the 5-fold approach, it achieved an accuracy of 94.1%, a balanced accuracy (BAC) of 92.18%, precision of 91.6%, recall of 90.61%, specificity of 93.75%, F1 score of 89.82%, and Intersection over Union (IoU) of 82.62%. In the 10-fold approach, stacking continued to demonstrate impressive results with an accuracy of 94.43%, BAC of 93.0%, precision of 92.03%, recall of 91.39%, specificity of 94.61%, F1 score of 91.23%, and IoU of 84.56%. In the leave-one-subject-out (LOSO) approach, the model continues to exhibit notable outcomes, achieving an accuracy of 91.6%, BAC of 90.27%, precision of 88.55%, recall of 87.96%, specificity of 92.59%, F1 score of 87.94%, and IoU of 78.69%. These results indicate that stacking and majority voting are crucial components of the CAD system, contributing significantly to the overall performance improvements. The proposed technology can help doctors assess which patients need more intensive clinical care.

Diffusion-Weighted Imaging Fluid-Attenuated Inversion Recovery Mismatch on Portable, Low-Field Magnetic Resonance Imaging Among Acute Stroke Patients.

For stroke patients with unknown time of onset, mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can guide thrombolytic intervention. However, access to MRI for hyperacute stroke is limited. Here, we sought to evaluate whether a portable, low-field (LF)-MRI scanner can identify DWI-FLAIR mismatch in acute ischemic stroke. Eligible patients with a diagnosis of acute ischemic stroke underwent LF-MRI acquisition on a 0.064-T scanner within 24 h of last known well. Qualitative and quantitative metrics were evaluated. Two trained assessors determined the visibility of stroke lesions on LF-FLAIR. An image coregistration pipeline was developed, and the LF-FLAIR signal intensity ratio (SIR) was derived. The study included 71 patients aged 71 ± 14 years and a National Institutes of Health Stroke Scale of 6 (interquartile range 3-14). The interobserver agreement for identifying visible FLAIR hyperintensities was high (κ = 0.85, 95% CI 0.70-0.99). Visual DWI-FLAIR mismatch had a 60% sensitivity and 82% specificity for stroke patients <4.5 h, with a negative predictive value of 93%. LF-FLAIR SIR had a mean value of 1.18 ± 0.18 <4.5 h, 1.24 ± 0.39 4.5-6 h, and 1.40 ± 0.23 >6 h of stroke onset. The optimal cut-point for LF-FLAIR SIR was 1.15, with 85% sensitivity and 70% specificity. A cut-point of 6.6 h was established for a FLAIR SIR <1.15, with an 89% sensitivity and 62% specificity. A 0.064-T portable LF-MRI can identify DWI-FLAIR mismatch among patients with acute ischemic stroke. Future research is needed to prospectively validate thresholds and evaluate a role of LF-MRI in guiding thrombolysis among stroke patients with uncertain time of onset. ANN NEUROL 2024;96:321-331.

Differentiation of hemispheric white matter lesions in migraine and multiple sclerosis with similar radiological features using advanced MRI.

White matter hyperintensities (WMHs), presented on T2-weighted or fluid-attenuated inversion recovery magnetic resonance imaging (MRI) sequences, are lesions in the human brain that can be observed in both migraine and multiple sclerosis (MS). Seventeen migraine patients and 15 patients with relapsing-remitting multiple sclerosis with WMHs, and 17 healthy subjects age-and sex-matched to the migraine group were prospectively enrolled and underwent conventional and advanced MRI studies with diffusion-and perfusion-weighted imaging and single voxel proton magnetic resonance spectroscopy. In both disease groups, elevated T2 relaxation time, apparent diffusion coefficient (ADC) values, and decreased N-acetyl-aspartate levels were found in the intralesional white matter compared to the contralateral normal-appearing white matter (NAWM), while there was no difference between the hemispheres of the control subjects. Migraine patients had the lowest intralesional creatine + phosphocreatine and myo-inositol (mI) values among the three groups, while patients with MS showed the highest intralesional T1 and T2 relaxation times, ADC, and mI values. In the contralateral NAWM, the same trend with mI changes was observed in migraineurs and MS patients. No differences in perfusion variables were observed in any groups. Our multimodal study showed that tissue damage is detectable in both diseases. Despite the differences in various advanced MRI measures, with more severe injury detected in MS lesions, we could not clearly differentiate the two white matter lesion types.

Artificial intelligence for volumetric measurement of cerebral white matter hyperintensities on thick-slice fluid-attenuated inversion recovery (FLAIR) magnetic resonance images from multiple centers

We aimed to develop a new artificial intelligence software that can automatically extract and measure the volume of white matter hyperintensities (WMHs) in head magnetic resonance imaging (MRI) using only thick-slice fluid-attenuated inversion recovery (FLAIR) sequences from multiple centers. We enrolled 1092 participants in Japan, comprising the thick-slice Private Dataset. Based on 207 randomly selected participants, neuroradiologists annotated WMHs using predefined guidelines. The annotated images of participants were divided into training (n = 138) and test (n = 69) datasets. The WMH segmentation model comprised a U-Net ensemble and was trained using the Private Dataset. Two other models were trained for validation using either both thin- and thick-slice MRI datasets or the thin-slice dataset alone. The voxel-wise Dice similarity coefficient (DSC) was used as the evaluation metric. The model trained using only thick-slice MRI showed a DSC of 0.820 for the test dataset, which is comparable to the accuracy of human readers. The model trained with the additional thin-slice dataset showed only a slightly improved DSC of 0.822. This automatic WMH segmentation model comprising a U-Net ensemble trained on a thick-slice FLAIR MRI dataset is a promising new method. Despite some limitations, this model may be applicable in clinical practice.

Simulation of acquisition shifts in T2 weighted fluid-attenuated inversion recovery magnetic resonance images to stress test artificial intelligence segmentation networks.

To provide a simulation framework for routine neuroimaging test data, which allows for "stress testing" of deep segmentation networks against acquisition shifts that commonly occur in clinical practice for T2 weighted (T2w) fluid-attenuated inversion recovery magnetic resonance imaging protocols. The approach simulates "acquisition shift derivatives" of MR images based on MR signal equations. Experiments comprise the validation of the simulated images by real MR scans and example stress tests on state-of-the-art multiple sclerosis lesion segmentation networks to explore a generic model function to describe the F1 score in dependence of the contrast-affecting sequence parameters echo time (TE) and inversion time (TI). The differences between real and simulated images range up to 19% in gray and white matter for extreme parameter settings. For the segmentation networks under test, the F1 score dependency on TE and TI can be well described by quadratic model functions (). The coefficients of the model functions indicate that changes of TE have more influence on the model performance than TI. We show that these deviations are in the range of values as may be caused by erroneous or individual differences in relaxation times as described by literature. The coefficients of the F1 model function allow for a quantitative comparison of the influences of TE and TI. Limitations arise mainly from tissues with a low baseline signal (like cerebrospinal fluid) and when the protocol contains contrast-affecting measures that cannot be modeled due to missing information in the DICOM header.

Dual Inversion Recovery Magnetic Resonance Imaging's Diagnostic Value for Estimating the Overall Load of Multiple Sclerosis Lesions and its Anatomical Distribution

B Background: In young adults, multiple sclerosis is a prevalent chronic inflammatory demyelinating condition. It is characterized by white matter affection, but many individuals also have significant gray matter involvement. A double inversion recovery pulse pattern was recently proposed to improve the detectability of multiple sclerosis lesions. Objectives: To evaluate the diagnostic value of double inversion recovery sequence in the detection of cortical and white matter multiple sclerosis plaques in different brain anatomical locations. Subjects and methods: A total of 37 patients with an established diagnosis of multiple sclerosis were included in this cross-sectional study. Brain MRI was done using double inversion recovery, T2 and FLAIR sequences. The number of lesions was counted and compared in the three sequences. Results: Dual Inversion Recovery sequence was highly significant and superior to both T2 and FLAIR sequences (P &lt; 0.001) in depicting the lesions regardless of anatomical distribution. Dual Inversion Recovery was significantly superior to T2 (P =&lt;0.001) and FLAIR (P =&lt;0.001) in detecting lesions in cortical and juxtacortical. However, Dual Inversion Recovery shows less periventricular and deep white matter lesions in comparison to T2 and FLAIR sequences. Conclusion: The Dual Inversion Recovery sequence detected more multiple sclerosis lesions in cortical, subcortical and infratentorial than the traditional T2W and FLAIR sequences. It also demonstrated greater delineation between the white matter, grey matter, and multiple sclerosis lesions, which became more easily visualized.

106 Characteristics of Cognitive Impairment in Moyamoya Disease

INTRODUCTION: Cognitive impairment in adult moyamoya disease (MMD) is thought to be the result of ischemic stroke; however, the presence and extent of cognitive decline in asymptomatic patients remain largely unknown. METHODS: After classification using T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), a total of 19 MMD patients with a history of cerebral infarction, 21 asymptomatic MMD patients, and 20 healthy controls matched for age, sex, and years of education were prospectively included in this study. A detailed neuropsychological evaluation of two moyamoya subgroups and normal controls was conducted. In addition, participants underwent arterial spin labeling and resting state fMRI sequences. RESULTS: Asymptomatic patients showed varying degrees of decline in intelligence (Raven’s Standard Progressive Matrices, P = 0.001), spatial imagination (mental rotation, P = 0.014), working memory (verbal working memory-backward digit span, P = 0.011), and computational ability (simple subtraction, P = 0.014; complex subtraction, P &lt; 0.001) compared with normal controls. MMD patients with cerebral infarction had more severe impairment in complex arithmetic (P = 0.027) and word short-term memory (P = 0.01) than those without symptoms. The asymptomatic MMD group also showed decreased CBF in the left anterior central and left inferior frontal gyri of the island fap with multiple node abnormalities in the brain network and reduced network connectivity. There was a significant association of these changes with cognitive decline in the MMD group. CONCLUSIONS: In asymptomatic MMD patients, a variety of cognitive impairments precedes the onset of clinical symptoms such as cerebral infarction, which may be a long-term complication of conservative treatment. Besides, disturbance of CBF and impaired brain network connections may be important causes of cognitive decline.

Diagnostic Utility of Contrast-Enhanced Fluid-Attenuated Inversion Recovery Magnetic Resonance Imaging in Intracranial Pathologies: Qualitative and Quantitative Analyses

Diagnostic Utility of Contrast-Enhanced Fluid-Attenuated Inversion Recovery Magnetic Resonance Imaging in Intracranial Pathologies: Qualitative and Quantitative Analyses

Patient-Specific Three-Dimensional-Printed and Bolus Material-Based Localization Grids for Magnetic Resonance Imaging-Guided Interventional Procedures

Abstract In view of the lack of commercially available localization grids for magnetic resonance imaging (MRI)-guided interventional procedures, two customizable and easily fabricable grids are proposed. The first one is a patient-specific three-dimensional-printed localization grid that incorporates MRI markers while the second one is a grid constructed with Superflex Transparent Bolus material. MRI scans were performed with the grids attached on an abdominal phantom. The patient-specific three-dimensional-printed grid is visible in T1-weighted, T2-weighted, proton density (PD) and fluid attenuated inversion recovery MR images, whereas the Superflex grid is visible only in T1-weighted and PD images. However, the Superflex grid offers the advantage of a simpler fabrication process and is more cost-effective. Both proposed localization grids can facilitate the determination of the optimal needle entry positions for MRI-guided interventional procedures, leading to reduced overall procedure time and improved efficiency.

In vivo PET of synaptic density as potential diagnostic marker for cognitive disorders: prospective comparison with current imaging markers for neuronal dysfunction and relation to symptomatology - study protocol

Background18F-FDG brain PET is clinically used for differential diagnosis in cognitive dysfunction of unclear etiology and for exclusion of a neurodegenerative cause in patients with cognitive impairment in late-life psychiatric disorders. 18F-FDG PET measures regional glucose metabolism, which represents a combination of neuronal/synaptic activity but also astrocytic activity and neuroinflammation. Recently, imaging of synaptic vesicle protein 2 A (SV2A) has become available and was shown to be a proxy of synaptic density. This prospective study will investigate the use of 18F-SynVesT-1 for imaging SV2A and its discriminative power for differential diagnosis in cognitive disorders in a head-to-head comparison to 18F-FDG PET. In addition, simultaneous PET/MR allows an evaluation of contributing factors and the additional value of advanced MRI imaging to FDG/SV2A PET imaging will be investigated. In this work, the study design and protocol are depicted.MethodsIn this prospective, multimodal imaging study, 110 patients with uncertain diagnosis of cognitive impairment who are referred for 18F-FDG PET brain imaging in their diagnostic work-up in a tertiary memory clinic will be recruited. In addition, 40 healthy volunteers (HV) between 18 and 85 years (M/F) will be included. All study participants will undergo simultaneous 18F-SynVesT-1 PET/MR and an extensive neuropsychological evaluation. Amyloid status will be measured by PET using 18FNAV4694, in HV above 50 years of age. Structural T1-weighted and T2-weighted fluid-attenuated inversion recovery MR images, triple-tagging arterial spin labeling (ASL) and resting-state functional MRI (rs-fMRI) will be obtained. The study has been registered on ClinicalTrials.gov (NCT05384353) and is approved by the local Research Ethics Committee.DiscussionThe main endpoint of the study will be the comparison of the diagnostic accuracy between 18F-SynVesT-1 and 18F-FDG PET in cognitive disorders with uncertain etiology and in exclusion of a neurodegenerative cause in patients with cognitive impairment in late-life psychiatric disorders. The strength of the relationship between cognition and imaging data will be assessed, as well as the potential incremental diagnostic value of including MR volumetry, ASL perfusion and rs-fMRI.

Small vessel cerebrovascular disease is associated with cognition in prospective Alzheimer’s clinical trial participants

BackgroundSecondary prevention clinical trials for Alzheimer’s disease (AD) target amyloid accumulation in asymptomatic, amyloid-positive individuals, but it is unclear to what extent other pathophysiological processes, such as small vessel cerebrovascular disease, account for participant performance on the primary cognitive outcomes in those trials. White matter hyperintensities are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) that reflect small vessel cerebrovascular disease. They are associated with cognitive functioning in older adults and with clinical presentation and course of AD, particularly when distributed in posterior brain regions. The purpose of this study was to examine to what degree regional WMH volume is associated with performance on the primary cognitive outcome measure in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study, a secondary prevention trial.MethodsData from 1791 participants (59.5% women, mean age (SD) 71.6 (4.74)) in the A4 study and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) companion study at the screening visit were used to quantify WMH volumes on T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Cognition was assessed with the preclinical Alzheimer cognitive composite (PACC). We tested the association of total and regional WMH volumes with PACC performance, adjusting for age, education, and amyloid positivity status, with general linear models. We also considered interactions between WMH and amyloid positivity status.ResultsIncreased frontal and parietal lobe WMH volume was associated with poorer performance on the PACC. While amyloid positivity was also associated with lower cognitive test scores, WMH volumes did not interact with amyloid positivity status.ConclusionThese results highlight the potential of small vessel cerebrovascular disease to drive AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered when evaluating outcome in trials, both as potential effect modifiers and as a possible target for intervention or prevention.

Cerebrovascular lesion loads and accelerated brain aging: insights into the cognitive spectrum.

White matter hyperintensities (WMHs) and cerebral microbleeds are widespread among aging population and linked with cognitive deficits in mild cognitive impairment (MCI), vascular MCI (V-MCI), and Alzheimer's disease without (AD) or with a vascular component (V-AD). In this study, we aimed to investigate the association between brain age, which reflects global brain health, and cerebrovascular lesion load in the context of pathological aging in diverse forms of clinically-defined neurodegenerative conditions. We computed brain-predicted age difference (brain-PAD: predicted brain age minus chronological age) in the Comprehensive Assessment of Neurodegeneration and Dementia cohort of the Canadian Consortium on Neurodegeneration in Aging including 70 cognitively intact elderly (CIE), 173 MCI, 88 V-MCI, 50 AD, and 47 V-AD using T1-weighted magnetic resonance imaging (MRI) scans. We used a well-established automated methodology that leveraged fluid attenuated inversion recovery MRIs for precise quantification of WMH burden. Additionally, cerebral microbleeds were detected utilizing a validated segmentation tool based on the ResNet50 network, utilizing routine T1-weighted, T2-weighted, and T2* MRI scans. The mean brain-PAD in the CIE cohort was around zero, whereas the four categories showed a significantly higher mean brain-PAD compared to CIE, except MCI group. A notable association trend between brain-PAD and WMH loads was observed in aging and across the spectrum of cognitive impairment due to AD, but not between brain-PAD and microbleed loads. WMHs were associated with faster brain aging and should be considered as a risk factor which imperils brain health in aging and exacerbate brain abnormalities in the context of neurodegeneration of presumed AD origin. Our findings underscore the significance of novel research endeavors aimed at elucidating the etiology, prevention, and treatment of WMH in the area of brain aging.