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  1. Article ; Online: Spatial patterns of elevated magnetic susceptibility in progressive apraxia of speech

    Ryota Satoh / Arvin Arani / Matthew L. Senjem / Joseph R. Duffy / Heather M. Clark / Rene L. Utianski / Hugo Botha / Mary M. Machulda / Clifford R. Jack, Jr / Jennifer L. Whitwell / Keith A. Josephs

    NeuroImage: Clinical, Vol 38, Iss , Pp 103394- (2023)

    2023  

    Abstract: Purpose: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder affecting the planning or programming of speech. Little is known about its magnetic susceptibility profiles indicative of biological processes such as iron deposition and ... ...

    Abstract Purpose: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder affecting the planning or programming of speech. Little is known about its magnetic susceptibility profiles indicative of biological processes such as iron deposition and demyelination. This study aims to clarify (1) the pattern of susceptibility in PAOS patients, (2) the susceptibility differences between the phonetic (characterized by predominance of distorted sound substitutions and additions) and prosodic (characterized by predominance of slow speech rate and segmentation) subtypes of PAOS, and (3) the relationships between susceptibility and symptom severity. Methods: Twenty patients with PAOS (nine phonetic and eleven prosodic subtypes) were prospectively recruited and underwent a 3 Tesla MRI scan. They also underwent detailed speech, language, and neurological evaluations. Quantitative susceptibility maps (QSM) were reconstructed from multi-echo gradient echo MRI images. Region of interest analysis was conducted to estimate susceptibility coefficients in several subcortical and frontal regions. We compared susceptibility values between PAOS and an age-matched control group and performed a correlation analysis between susceptibilities and an apraxia of speech rating scale (ASRS) phonetic and prosodic feature ratings. Results: The magnetic susceptibility of PAOS was statistically greater than that of controls in subcortical regions (left putamen, left red nucleus, and right dentate nucleus) (p < 0.01, also survived FDR correction) and in the left white-matter precentral gyrus (p < 0.05, but not survived FDR correction). The prosodic patients showed greater susceptibilities than controls in these subcortical and precentral regions. The susceptibility in the left red nucleus and in the left precentral gyrus correlated with the prosodic sub-score of the ASRS. Conclusion: Magnetic susceptibility in PAOS patients was greater than controls mainly in the subcortical regions. While larger samples are needed before QSM is considered ...
    Keywords Apraxia of speech ; Progressive apraxia of speech ; Magnetic resonance imaging ; Quantitative susceptibility mapping ; Iron ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 410
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Evidence against a temporal association between cerebrovascular disease and Alzheimer’s disease imaging biomarkers

    Petrice M. Cogswell / Emily S. Lundt / Terry M. Therneau / Carly T. Mester / Heather J. Wiste / Jonathan Graff-Radford / Christopher G. Schwarz / Matthew L. Senjem / Jeffrey L. Gunter / Robert I. Reid / Scott A. Przybelski / David S. Knopman / Prashanthi Vemuri / Ronald C. Petersen / Clifford R. Jack

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 12

    Abstract: Abstract 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. ... ...

    Abstract Abstract 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, R2 = 32%). These findings support a strong mechanistic relationship between amyloid and tau aggregation, but not between WMH or FA and amyloid or tau PET.
    Keywords Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Neuroimaging correlates of gait abnormalities in progressive supranuclear palsy

    Irene Sintini / Kenton Kaufman / Hugo Botha / Peter R. Martin / Stacy R. Loushin / Matthew L. Senjem / Robert I. Reid / Christopher G. Schwarz / Clifford R. Jack Jr / Val J. Lowe / Keith A. Josephs / Jennifer L. Whitwell / Farwa Ali

    NeuroImage: Clinical, Vol 32, Iss , Pp 102850- (2021)

    2021  

    Abstract: Progressive supranuclear palsy is a neurodegenerative disorder characterized primarily by tau inclusions and neurodegeneration in the midbrain, basal ganglia, thalamus, premotor and frontal cortex. Neurodegenerative change in progressive supranuclear ... ...

    Abstract Progressive supranuclear palsy is a neurodegenerative disorder characterized primarily by tau inclusions and neurodegeneration in the midbrain, basal ganglia, thalamus, premotor and frontal cortex. Neurodegenerative change in progressive supranuclear palsy has been assessed using MRI. Degeneration of white matter tracts is evident with diffusion tensor imaging and PET methods have been used to assess brain metabolism or presence of tau protein deposits. Patients with progressive supranuclear palsy present with a variety of clinical syndromes; however early onset of gait impairments and postural instability are common features. In this study we assessed the relationship between multimodal imaging biomarkers (i.e., MRI atrophy, white matter tracts degeneration, flortaucipir-PET uptake) and laboratory-based measures of gait and balance abnormalities in a cohort of nineteen patients with progressive supranuclear palsy, using univariate and multivariate statistical analyses. The PSP rating scale and its gait midline sub-score were strongly correlated to gait abnormalities but not to postural imbalance. Principal component analysis on gait variables identified velocity, stride length, gait stability ratio, length of gait phases and dynamic stability as the main contributors to the first component, which was associated with diffusion tensor imaging measures in the posterior thalamic radiation, external capsule, superior cerebellar peduncle, superior fronto-occipital fasciculus, body and splenium of the corpus callosum and sagittal stratum, with MRI volumes in frontal and precentral regions and with flortaucipir-PET uptake in the precentral gyrus. The main contributor to the second principal component was cadence, which was higher in patients presenting more abnormalities on mean diffusivity: this unexpected finding might be related to compensatory gait strategies adopted in progressive supranuclear palsy. Postural imbalance was the main contributor to the third principal component, which was related to flortaucipir-PET ...
    Keywords Progressive supranuclear palsy ; Diffusion tensor imaging ; Gait ; Balance ; MRI ; PET ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 616
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: TDP-43-associated atrophy in brains with and without frontotemporal lobar degeneration

    Marina Buciuc / Peter R. Martin / Nirubol Tosakulwong / Melissa E. Murray / Leonard Petrucelli / Matthew L. Senjem / Anthony J. Spychalla / David S. Knopman / Bradley F. Boeve / Ronald C. Petersen / Joseph E. Parisi / R. Ross Reichard / Dennis W. Dickson / Clifford R. Jack, Jr. / Jennifer L. Whitwell / Keith A. Josephs

    NeuroImage: Clinical, Vol 34, Iss , Pp 102954- (2022)

    2022  

    Abstract: Transactive response DNA-binding protein of ∼43 kDa (TDP-43), a primary pathologic substrate in tau-negative frontotemporal lobar degeneration (FTLD), is also often found in the brains of elderly individuals without FTLD and is a key player in the ... ...

    Abstract Transactive response DNA-binding protein of ∼43 kDa (TDP-43), a primary pathologic substrate in tau-negative frontotemporal lobar degeneration (FTLD), is also often found in the brains of elderly individuals without FTLD and is a key player in the process of neurodegeneration in brains with and without FTLD. It is unknown how rates and trajectories of TDP-43-associated brain atrophy compare between these two groups. Additionally, non-FTLD TDP-43 inclusions are not homogeneous and can be divided into two morphologic types: type-α and neurofibrillary tangle-associated type-β. Therefore, we explored whether neurodegeneration also varies due to the morphologic type. In this longitudinal retrospective study of 293 patients with 843 MRI scans spanning over ∼10 years, we used a Bayesian hierarchical linear model to quantify similarities and differences between the non-FTLD TDP-43 (type-α/type-β) and FTLD-TDP (n = 68) in both regional volume at various timepoints before death and annualized rate of atrophy. Since Alzheimer’s disease (AD) is a frequent co-pathology in non-FTLD TDP-43, we further divided types α/β based on presence/absence of intermediate-high likelihood AD: AD-TDP type-β (n = 90), AD-TDP type-α (n = 104), and Pure-TDP (n = 31, all type-α). FTLD-TDP was associated with faster atrophy rates in the inferior temporal lobe and temporal pole compared to all non-FTLD TDP-43 groups. The atrophy rate in the frontal lobe was modulated by age with younger FTLD-TDP having the fastest rates. Older FTLD-TDP showed a limbic predominant pattern of neurodegeneration. AD-TDP type-α showed faster rates of hippocampal atrophy and smaller volumes of amygdala, temporal pole, and inferior temporal lobe compared to AD-TDP type-β. Pure-TDP was associated with slowest rates and less atrophy in all brain regions. The results suggest that there are differences and similarities in longitudinal brain volume loss between FTLD-TDP and non-FTLD TDP-43. Within FTLD-TDP age plays a role in which brain regions are the most affected. ...
    Keywords Alzheimer’s disease ; TDP-43 ; MRI ; LATE ; Old age FTLD ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 616
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Considerations for Performing Level-2 Centiloid Transformations for Amyloid PET SUVR values

    Christopher G. Schwarz / Nirubol Tosakulwong / Matthew L. Senjem / Jeffrey L. Gunter / Terry M. Therneau / Prashanthi Vemuri / Val J. Lowe / Clifford R. Jack

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 6

    Abstract: Abstract The Centiloid Project describes a post-hoc data transformation to standardize amyloid PET measurements to enable direct data comparisons across sites and studies using differing acquisition/analysis methods. It uses linear regression that ... ...

    Abstract Abstract The Centiloid Project describes a post-hoc data transformation to standardize amyloid PET measurements to enable direct data comparisons across sites and studies using differing acquisition/analysis methods. It uses linear regression that transforms values using different measurement scales to match those from a standard Centiloid unit scale. Our group’s measurement method differs from the Centiloid’s standard method in both acquisition and analysis methods. In this work we examine multiple variations for performing these transformations and compare several approaches. We hypothesized that using Deming regression, which accounts for error on both axes, would produce a more optimal transformation than the recommended standard linear regression. We also examined the effects of performing separate regressions for differences in acquisition and analysis methods, rather than a direct single-regression approach. Our results found that all transformation approaches had very similar performance and were within the recommended tolerance thresholds.
    Keywords Medicine ; R ; Science ; Q
    Subject code 310
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: 18F-FDG PET-CT pattern in idiopathic normal pressure hydrocephalus

    Ryan A. Townley / Hugo Botha / Jonathan Graff-Radford / Bradley F. Boeve / Ronald C. Petersen / Matthew L. Senjem / David S. Knopman / Val Lowe / Clifford R. Jack, Jr / David T. Jones

    NeuroImage: Clinical, Vol 18, Iss , Pp 897-

    2018  Volume 902

    Abstract: Background: Idiopathic normal pressure hydrocephalus (iNPH) is an important and treatable cause of neurologic impairment. Diagnosis is complicated due to symptoms overlapping with other age related disorders. The pathophysiology underlying iNPH is not ... ...

    Abstract Background: Idiopathic normal pressure hydrocephalus (iNPH) is an important and treatable cause of neurologic impairment. Diagnosis is complicated due to symptoms overlapping with other age related disorders. The pathophysiology underlying iNPH is not well understood. We explored FDG-PET abnormalities in iNPH patients in order to determine if FDG-PET may serve as a biomarker to differentiate iNPH from common neurodegenerative disorders. Methods: We retrospectively compared 18F-FDG PET-CT imaging patterns from seven iNPH patients (mean age 74 ± 6 years) to age and sex matched controls, as well as patients diagnosed with clinical Alzheimer's disease dementia (AD), Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD), and behavioral variant frontotemporal dementia (bvFTD). Partial volume corrected and uncorrected images were reviewed separately. Results: Patients with iNPH, when compared to controls, AD, DLB/PDD, and bvFTD, had significant regional hypometabolism in the dorsal striatum, involving the caudate and putamen bilaterally. These results remained highly significant after partial volume correction. Conclusions: In this study, we report a FDG-PET pattern of hypometabolism in iNPH involving the caudate and putamen with preserved cortical metabolism. This pattern may differentiate iNPH from degenerative diseases and has the potential to serve as a biomarker for iNPH in future studies. These findings also further our understanding of the pathophysiology underlying the iNPH clinical presentation. Keywords: FDG-PET, Normal pressure hydrocephalus, Hypometabolism, Caudate, Biomarker
    Keywords Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 610
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Brain volume and flortaucipir analysis of progressive supranuclear palsy clinical variants

    Jennifer L. Whitwell / Nirubol Tosakulwong / Hugo Botha / Farwa Ali / Heather M. Clark / Joseph R. Duffy / Rene L. Utianski / Chase A. Stevens / Stephen D. Weigand / Christopher G. Schwarz / Matthew L. Senjem / Clifford R. Jack / Val J. Lowe / J. Eric Ahlskog / Dennis W. Dickson / Keith A. Josephs

    NeuroImage: Clinical, Vol 25, Iss , Pp - (2020)

    2020  

    Abstract: Background and purpose: Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that is associated with different clinical variants, including PSP-Richardson's syndrome (PSP-RS), PSP-parkinsonism (PSP-P), PSP-corticobasal syndrome (PSP-CBS), ...

    Abstract Background and purpose: Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that is associated with different clinical variants, including PSP-Richardson's syndrome (PSP-RS), PSP-parkinsonism (PSP-P), PSP-corticobasal syndrome (PSP-CBS), PSP-frontal (PSP-F), PSP-progressive gait freezing (PSP-PGF) and PSP-speech/language (PSP-SL). While PSP-RS has been well-characterized on neuroimaging, the characteristics of the other atypical variants are less well defined and it is unknown how they compare to each other or relate to neuropathology. We aimed to assess and compare regional atrophy on MRI and [18F]flortaucipir uptake on PET across PSP variants. Materials and methods: 105 PSP patients (53 PSP-RS, 23 PSP-SL, 12 PSP-P, 8 PSP-CBS, 5 PSP-F and 4 PSP-PGF) underwent volumetric MRI, with 59 of these also undergoing flortaucipir PET. Voxel-level and region-level analyses were performed comparing PSP variants to 30 controls and to each other. Semi-quantitative tau burden measurements were also performed in 21 patients with autopsy-confirmed PSP. Results: All variants showed evidence for atrophy or increased flortaucipir uptake in striatum, globus pallidus and thalamus. Superior cerebellar peduncle volume loss was only observed in PSP-RS, PSP-CBS and PSP-F. Volume loss in the frontal lobes was observed in PSP-SL, PSP-CBS and PSP-F, with these variants also showing highest cortical tau burden at autopsy. The PSP-P and PSP-PGF variants showed more restricted patterns of neurodegeneration predominantly involving striatum, globus pallidus, subthalamic nucleus and thalamus. The PSP-SL variant showed greater volume loss and flortaucipir uptake in supplementary motor area and motor cortex compared to all other variants, but showed less involvement of subthalamic nucleus and midbrain. Compared to PSP-RS, PSP-P had larger midbrain volume and greater flortaucipir uptake in putamen. Conclusion: The PSP variants have different patterns of involvement of subcortical circuitry, perhaps suggesting different patterns of ...
    Keywords Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 610 ; 616
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Comparison of [18F]Flutemetamol and [11C]Pittsburgh Compound-B in cognitively normal young, cognitively normal elderly, and Alzheimer's disease dementia individuals

    Val J. Lowe / Emily Lundt / David Knopman / Matthew L. Senjem / Jeffrey L. Gunter / Christopher G. Schwarz / Bradley J. Kemp / Clifford R. Jack, Jr / Ronald C. Petersen

    NeuroImage: Clinical, Vol 16, Iss , Pp 295-

    2017  Volume 302

    Abstract: Background: Understanding the variation in uptake between different amyloid PET tracers is important to appropriately interpret data using different amyloid tracers. Therefore, we compared the uptake differences in [18F]Flutemetamol (FMT) and [11C]PiB ( ... ...

    Abstract Background: Understanding the variation in uptake between different amyloid PET tracers is important to appropriately interpret data using different amyloid tracers. Therefore, we compared the uptake differences in [18F]Flutemetamol (FMT) and [11C]PiB (PiB) PET in the same people. Methods: Structural MRI, FMT PET and PiB PET were each performed in 30 young cognitively normal (yCN), 31 elderly cognitively normal (eCN) and 21 Alzheimer's disease dementia (AD) participants. PiB and FMT images for each participant were compared quantitatively using voxel- and region-based analyses. Region of interest (ROI) analyses included comparisons of grey matter (GM) regions as well as white matter (WM) regions. Regional comparisons of each tracer between different groups and comparisons of the two modalities within the different groups were performed. To compare mean SUVr between modalities, and between diagnostic groups, we used paired t-tests and Student's t-test, respectively. We also compared the ability of the two tracers to discriminate between diagnostic groups using AUROC estimates. The effect of using different normalization regions on SUVr values was also evaluated. Results: Both FMT and PiB showed greater uptake throughout GM structures in AD vs. eCN or yCN. In all dual-modality group comparisons (FMT vs. PiB in yCN, eCN, and AD), greater WM uptake was seen with FMT vs. PiB. In yCN and eCN greater diffuse GM uptake was seen with FMT vs. PiB. When comparing yCN to eCN within each tracer, greater WM uptake was seen in eCN vs yCN. Conclusions: Flutemetamol and PiB show similar topographical GM uptake in AD and CN participants and the tracers show comparable group discrimination. Greater WM accumulation with FMT suggests that quantitative differences vs. PiB will be apparent when using WM or GM as a reference region. Both imaging tracers demonstrate increased WM uptake in older people. These findings suggest that using different amyloid tracers or different methods of analyses in serial brain imaging in an individual ...
    Keywords Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: FDG PET metabolic signatures distinguishing prodromal DLB and prodromal AD

    Kejal Kantarci / Bradley F. Boeve / Scott A. Przybelski / Timothy G. Lesnick / Qin Chen / Julie Fields / Christopher G. Schwarz / Matthew L. Senjem / Jeffrey L. Gunte / Clifford R. Jack / Paul Min / Manoj Jain / Toji Miyagawa / Rodolfo Savica / Jonathan Graff-Radford / Hugo Botha / David T. Jones / David S. Knopman / Neill Graff-Radford /
    Tanis J. Ferman / Ronald C. Petersen / Val J. Lowe

    NeuroImage: Clinical, Vol 31, Iss , Pp 102754- (2021)

    2021  

    Abstract: Background and Purpose: Patients with dementia with Lewy bodies (DLB) are characterized by hypometabolism in the parieto–occipital cortex and the cingulate island sign (CIS) on 18F-fluorodeoxyglucose (FDG) PET. Whether this pattern of hypometabolism is ... ...

    Abstract Background and Purpose: Patients with dementia with Lewy bodies (DLB) are characterized by hypometabolism in the parieto–occipital cortex and the cingulate island sign (CIS) on 18F-fluorodeoxyglucose (FDG) PET. Whether this pattern of hypometabolism is present as early as the prodromal stage of DLB is unknown. We investigated the pattern of hypometabolism in patients with mild cognitive impairment (MCI) who progressed to probable DLB compared to MCI patients who progressed to Alzheimer’s disease (AD) dementia and clinically unimpaired (CU) controls. Methods: Patients with MCI from the Mayo Clinic Alzheimer’s Disease Research Center who underwent FDG PET at baseline and progressed to either probable DLB (MCI-DLB; n = 17) or AD dementia (MCI-AD; n = 41) during follow-up, and a comparison cohort of CU controls (n = 100) were included. Results: Patients with MCI-DLB had hypometabolism in the parieto-occipital cortex extending into temporal lobes, substantia nigra and thalamus. When compared to MCI-AD, medial temporal and posterior cingulate metabolism were preserved in patients with MCI-DLB, accompanied by greater hypometabolism in the substantia nigra in MCI-DLB compared to MCI-AD. In distinguishing MCI-DLB from MCI-AD at the maximum value of Youden’s index, CIS ratio was highly specific (90%) but not sensitive (59%), but a higher medial temporal to substantia nigra ratio was both sensitive (94%) and specific (83%). Conclusion: FDG PET is a potential biomarker for the prodromal stage of DLB. A higher medial temporal metabolism and CIS ratio, and lower substantia nigra metabolism have additive value in distinguishing prodromal DLB and AD.
    Keywords FDG PET ; Mild cognitive impairment ; Demenia with Lewy bodies ; Alzheimer's disease ; Cingulate island sign ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Regional brain stiffness changes across the Alzheimer's disease spectrum

    Matthew C. Murphy / David T. Jones / Clifford R. Jack Jr. / Kevin J. Glaser / Matthew L. Senjem / Armando Manduca / Joel P. Felmlee / Rickey E. Carter / Richard L. Ehman / John Huston III

    NeuroImage: Clinical, Vol 10, Iss C, Pp 283-

    2016  Volume 290

    Abstract: Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of ...

    Abstract Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD) spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology.
    Keywords MR elastography ; Brain stiffness ; Regional ; Alzheimer's disease ; Functional connectivity ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 610
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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