ISSN# 1545-4428 | Published date: 19 April, 2024
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At-A-Glance Session Detail
   
Mapping Brain Myelin & Metabolites
Digital Poster
Neuro
Monday, 06 May 2024
Exhibition Hall (Hall 403)
16:00 -  17:00
Session Number: D-100
No CME/CE Credit

Computer #
2028.
1Multiparametric Metabolic Imaging of Leukoencephalopathy at 7T: A Case Study
Paul S Jacobs1, Neil E Wilson1, Anshuman Swain1, Bailey Spangler2, Madeleine Seitz2, Allen Fu2, Jennifer Orthmann-Murphy3, Matthew K Schindler3, and Ravinder Reddy1
1Center for Advanced Metabolic Imaging in Precision Medicine, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Penn Statistics in Imaging and Visualization Endeavour, Department of Biostatistics, Epidemiology, & Informatics, University of Pennsylvania, Philadelphia, PA, United States, 3Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States

Keywords: White Matter, CEST & MT

Motivation: Standard structural MR imaging techniques are not able to provide information on the metabolic state of white matter lesion. Specialized imaging techniques such as NOE and GluCEST can complement these conventional images by leveraging larger chemical shifts at 7T. 

Goal(s): To observe potential NOE and GluCEST contrast differences in a leukoencephalopathy patient at 7T.

Approach: GluCEST and NOE images were acquired at 7T. NOE experimental z-spectral data was fit with multi-pool Lorentzian fitting to produce five individual pool fits.

Results: DS, MT, and rNOE differentiated white matter changes as well as GluCEST changes in the gray matter in a leukoencephalopathy patient. 

Impact: This method of ultra-high field MR imaging for patients with demyelinating conditions can provide complementary metabolic information to standard structural imaging that, when tracked longitudinally, can yield improved diagnostic outcomes and understanding of disease mechanism for this patient population.

2029.
2In Vivo Reproducibility of tNOE of Human Brain Using Tx/Rx Coil at 3T
Blake Benyard1, Dushyant Kumar1, Neil E Wilson1, and Ravinder Reddy1
1Center for Metabolic Imaging in Precision Medicine (CAMIPM), Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

Keywords: White Matter, Magnetization transfer, NOE

Motivation: Nuclear Overhauser Effect (NOE) is based on dipolar cross relaxation mechanism that enables the indirect detection of aliphatic protons via the water proton signal. This work focuses on determining the reproducibility of the transient-Nuclear-Overhauser-Effect (tNOE) of the healthy human brain at 3 Tesla.    
 

Goal(s): To establish reproducibility of tNOE in the brain regions of healthy subjects at 3T.

Approach: We scanned three healthy subjects multiple times to determine inter-day reproducibility of tNOE on 3T.

Results: The inter-subject coefficient of variations (CoV) of tNOE from GM and WM were 5.12% and 3.97%, respectively. The intra-subject tNOE CoV range for GM and WM was 0.24%-4.0%.  

Impact: This work will facilitate the use of tNOE at 3T to investigate macromolecular (lipid and proteins) derangements in different diseases with significantly reduced scan time and improved specificity compared to steady state NOE.    

2030.
3Simultaneous Assessment of Microstructural integrity and Metabolite Profile from Superior Longitudinal Fasciculus in Normal Healthy Brains
Archith Rajan1, Mauro Hanaoka1, Laiz Laura de Godoy1, Daniel Gewolb1, Elizabeth Dutweiler1, Sulaiman Sheriff2, Harish Poptani3, Suyash Mohan1, and Sanjeev Chawla1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Radiology, University of Miami, Miami, FL, United States, 3Centre for Preclinical Imaging, University of Liverpool, Liverpool, United Kingdom

Keywords: White Matter, Brain, Whole brain spectroscopic imaging, neurite orientation distribution and density imaging, Superior longitudinal fasciculus

Motivation: Superior longitudinal fasciculus (SLF) is critical in multiple normal functions. It is imperative to co-localize white-matter tract of SLF with metabolite maps to facilitate simultaneous analysis of microstructural integrity and metabolite alterations.

Goal(s): To evaluate relationships among metabolite ratios and diffusion MRI derived parameters along the path of SLF in normal healthy adults.

Approach: The associations between whole brain spectroscopy derived Cho/Cr, Cho/NAA ratios and diffusion MRI derived FA, MD, fICVF, fIso and ODI parameters were assessed along the length of SLF segments II-III.

Results: Strong significant correlations between Cho/Cr and Cho/NAA ratios and FA, MD, ficvf were observed.

Impact: Diffusion MRI and whole brain spectroscopy could be used to study the covariation of white matter microstructure and metabolism. Multiparametric normative tract profiles established over larger cohorts could serve as the basis for early detection of white matter anomalies.

2031.
4GABA in the anterior cingulate cortex mediates the association of white matter hyperintensities with executive function
Xiaona Fu1, Peng Sun2, Xinli Zhang1, Dongyong Zhu1, Qian Qin1, Jue Lu1, and Jing Wang1
1Department of Radiology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology, Wuhan, China, 2Clinical & Technical Support, Philips Healthcare, Beijing 100600, China, Beijing, China

Keywords: White Matter, White Matter, Gamma-aminobutyric acid

Motivation: The alteration of cortical GABA levels in WMH patients and whether it mediates the association of WMH volume with executive function remain unclear

Goal(s): We investigated the cortical GABA levels, and whether cortical GABA mediates the association between WMH and executive function in the WMH people.

Approach: We used the independent samples test,general linear model,partial correlation analyses and mediation analysis.

Results: Patients with moderate to severe WMH showed lower GABA+/Cr in the anterior cingulate cortex (ACC) and worse executive function than mild WMH patients. And  the GABA level in ACC mediates the association between white matter hyperintensities and executive function in WMH patients.

Impact: The GABA+/Cr level in the the anterior cingulate cortex had a critical role. And it mediates the association between white matter hyperintensities and executive function in the WMH patients.

2032.
51H-MRSI of white matter in cognitively unimpaired elderly for the detection of early Alzheimer’s disease pathological changes
Anna M Chen1,2,3, Helena Zheng1,2, Rosemary Peralta1,2, Mia Gajdošík1,2, Dishari Azad4, Ajax George1,2, Henry Rusinek1,2, Allal Boutajangout5,6, Sinyeob Ahn7, Ricardo Osorio4, and Ivan I Kirov1,2,3,6
1Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States, 2Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States, 3Vilcek Institute of Graduate Biomedical Sciences, New York University Grossman School of Medicine, New York, NY, United States, 4Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, United States, 5Department of Neuroscience and Physiology, New York University Grossman School of Medicine, New York, NY, United States, 6Department of Neurology, New York University Grossman School of Medicine, New York, NY, United States, 7Siemens Medical Solutions USA Inc., Malvern, PA, United States

Keywords: White Matter, White Matter, Aging, Alzheimer's Disease, Spectroscopy

Motivation: APOE4 has been linked to increased amyloid and tau deposition and microstructural WM changes in Alzheimer’s, but despite the major role of APOE in myelination, whether WM metabolism is altered in individuals at risk for Alzheimer’s remains unknown.

Goal(s): To examine if choline, a constituent of myelin and a marker of membrane turnover, is associated with APOE4, CSF p-tau181 (a marker of tau burden), and WM volume (a marker of neurodegeneration).

Approach: Cognitively unimpaired elderly with and without APOE4 underwent 1H-MRSI. Relationships between WM choline, APOE4, tau, and WM volume were assessed.

Results: No associations were found between WM choline and any marker.

Impact: WM metabolism is not associated with genotype, tau, or neurodegeneration in healthy elderly, but given that amyloid deposition is the earliest Alzheimer’s pathological hallmark, additional investigations with amyloid biomarkers are needed to better characterize WM metabolism in the preclinical stage.

2033.
6White Matter Damage and Myelin Loss in Rare PolyG Diseases: A 3T MRI Pilot Study
Justin T Hsieh1, Septian Hartono2,3,4, Ling Ling Chan2,5, Cornelia Laule6,7,8,9, Adeline Su Lyn Ng4, Eng King Tan2,4, Jayne Yi Tan4, and Tchoyoson CC Lim1,2
1Department of Neuroradiology, National Neuroscience Institute, Singapore, Singapore, 2Duke-NUS Medical School, Singapore, Singapore, 3Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore, 4Department of Neurology, National Neuroscience Institute, Singapore, Singapore, 5Department of Diagnostic Radiology, Singapore General Hospital, SINGAPORE, Singapore, 6Department of Radiology, University of British Columbia, Vancouver, BC, Canada, 7Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, 8Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, 9International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada

Keywords: White Matter, Diffusion/other diffusion imaging techniques, myelin, brain, myelin water imaging, diffusion

Motivation: Literature suggests that white matter (WM) may be specifically affected in polyG diseases, a novel class of genetic neurodegenerative diseases including fragile X-associated tremor/ataxia syndrome (FXTAS) and neuronal intranuclear inclusion disease (NIID).

Goal(s): To use advanced MRI to characterize WM in polyG disease.

Approach: 3T myelin water imaging and diffusion tensor imaging in participants with FXTAS and NIID.

Results: FXTAS and NIID demonstrated diffuse cerebral WM damage and myelin loss. Middle cerebellar peduncle (MCP) changes were seen in FXTAS, but not in NIID. Diffusion hyperintense foci in the MCP (FXTAS) and frontal WM (FXTAS and NIID) matched foci of highest dysmyelination.

Impact: Fragile X-associated tremor/ataxia syndrome and neuronal intranuclear inclusion disease show diffuse cerebral white matter abnormalities and myelin damage, and spatially differential changes in the frontal white matter and middle cerebellar peduncle.

2034.
7Direct myelin imaging using a 3D double adiabatic inversion recovery prepared ultrashort echo time (3D DIR-UTE) cones sequence
Jiyo S Athertya1, James Lo1,2, Qingbo Tang3, Kenichiro Doi1, Soo Hyun Shin1, Dina Moazamian1, Melissa Lou1, Arya Suprana1,2, Bhavsimran Singh Malhi1, Eric Y Chang1,3, Jiang Du1,2,3, and Yajun Ma1
1UCSD, San Diego, CA, United States, 2Dept of Bioengineering, UCSD, San Diego, CA, United States, 3Radiology Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, United States

Keywords: White Matter, White Matter, UTE imaging, Myelin

Motivation: Many neurological disorders are characterized by myelin damage and loss. Robust long T2 suppression is of critical importance for accurate myelin quantification due to myelin's low proton densities.  

Goal(s): To develop a new UTE imaging approach that enables sufficient long T2 suppression for selective myelin imaging.

Approach: A 3D DIR-UTE sequence was developed for selective myelin imaging on a 3T clinical scanner. The technical feasibility was tested by phantom and in vivo studies.

Results: The long T2 signals were sufficiently suppressed with the DIR scheme. The myelin proton fraction in white matter regions quantified by the DIR-UTE was 5.42±0.35%.

Impact: The long T2 signals were sufficiently suppressed with the DIR scheme. The myelin proton fraction in white matter regions quantified by the DIR-UTE was 5.42±0.35%.

2035.
8Selective imaging of myelin based on phase transition using a 3D adiabatic inversion recovery prepared ultrashort echo time (3D IR-UTE) sequence
Jiyo S Athertya1, Bhavsimran Singh Malhi1, Hyungseok Jang1, Sam Sedaghat1, Soo Hyun Shin1, Eric Y Chang1,2, Yajun Ma1, and Jiang Du1,2,3
1UCSD, San Diego, CA, United States, 2Radiology Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, United States, 3Dept of Bioengineering, UCSD, San Diego, CA, United States

Keywords: White Matter, White Matter

Motivation: There is a need for selective myelin imaging with minimal contamination from long-T2 water components.

Goal(s): To develop a new contrast mechanism for direct visualization of myelin using a three-dimensional adiabatic inversion recovery prepared ultrashort echo time (3D IR-UTE) sequence.

Approach: We employed the long-T2 signal phase transition in 3D dual-echo IR-UTE imaging to find the optimal inversion time (TI) necessary to null water signals for selective myelin imaging in a clinical 3T scanner. 

Results: Myelin signal could be selectively detected by 3D IR-UTE sequence based on long-T2 phase transition and optimal TI  for both ex vivo and in vivo brains.

Impact: The 3D IR-UTE sequence allows direct imaging of myelin, which is important for accurate diagnosis and assessment of multiple sclerosis (MS), Alzheimer’s disease (AD), and other neurological diseases.

2036.
9Characterizing Tissue Relaxation and Magnetization Transfer in Fresh, Thawed, and Fixed White Matter Tissue Samples
Amaya Murguia1, Scott D. Swanson2, Ulrich Scheven3, Jon-Fredrik Nielsen2,4, Jeffrey A. Fessler1,2,4, and Navid Seraji-Bozorgzad5
1Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI, United States, 2Radiology, University of Michigan, Ann Arbor, MI, United States, 3Mechanical Engineering, University of Michigan, Ann Arbor, MI, United States, 4Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States, 5Neurology, University of Michigan, Ann Arbor, MI, United States

Keywords: White Matter, White Matter

Motivation: Studying ex vivo tissue requires preservation by formalin-fixation or freezing.  Effects of these methods on tissue parameters compared to fresh tissue is unknown.

Goal(s): We investigated how freezing/thawing and fixation affect T1, T2, and MT properties in brain tissue. We created a protocol to apply MR methods (T2-MESE, biexponential T1, qMT, ihMT, NODDI) to pathology specimens in the Michigan Alzheimer’s Disease Research Center (MADRC) repository. 

Approach: We scanned the same ex vivo sheep brain samples fresh, frozen/thawed, and fixed, and compared their relaxation and MT properties.

Results: Effects of fixation are most prominent in white matter and especially influence T1 and T2 relaxation.

Impact: Thawed tissue exhibits more similar relaxation and MT properties to fresh tissue than fixed tissue does. In MR studies that use ex vivo tissue samples, such as those correlating MR to histology, thawed tissue may be preferable to formalin-fixed.

2037.
10Application of B1+ corrected data-driven myelin water imaging for the diagnosis of multiple sclerosis pathology in normal appearing tissue
Sharon Zlotzover1, Dvir Radunsky1, Dominique Ben-Ami Reichman2,3, Shai Shrot2,3, Chen Hoffmann2,3, and Noam Ben-Eliezer1,4,5
1Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel, 2Department of Diagnostic Imaging, Sheba Medical Center, Ramat Gan, Israel, 3Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, 4Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel, 5Center for Advanced Imaging Innovation and Research, New York University Langone Medical Center, New York, NY, United States

Keywords: White Matter, Quantitative Imaging, myelin water imaging, multicomponent analysis, multiple sclerosis, quantitative MRI, qMRI, white matter

Motivation: Multicomponent T2 (mcT2) analysis is the go-to tool for mapping myelin in vivo. Resolving T2 spectra, however, is highly challenging due to substantial ambiguity in the multidimensional space of microstructural configurations.

Goal(s): Accurate and reproducible myelin water imaging.

Approach: A spatially-global data-driven mcT2 analysis was employed, relying on the identification of tissue-specific mcT2 configurations prior to performing voxel-wise analysis. A new scheme was developed for correcting transmit field (B1+) inhomogeneities.

Results: Successful application of the data-driven technique is demonstrated on numerical phantom, healthy volunteers, and for identifying pathology in normal-appearing tissue of subjects with multiple sclerosis.

Impact: The data-driven approach constitutes a new paradigm for multi-component T2 fitting, yielding unprecedented accuracy and high robustness. Application on MS patients’ data highlights the potential of data-driven MWF values as a biomarker for pathology in normal appearing tissue.

2038.
11Development of numerical phantom converting from electron microscopic analysis to multi-component water fraction for MRI simulator.
Ryuji Ohshiro1, Yuki Kanazawa1, Akihiro Haga1, and Masafumi Harada1
1Tokushima University, Tokushima, Japan

Keywords: White Matter, Simulations

Motivation: To improve the accuracy of myelin water fraction (MWF) calculations.

Goal(s): To develop multi-component phantom for MRI simulators and to validate the accuracy depending on pulse sequences and imaging parameter settings.

Approach: First, five different electron micrographs of the normal central nervous system (CNS) were divided into two regions (my and ax/ie), and the percentage of each component was calculated. Second, each proton density (PD) was set as a percentage of the divided area. 

Results: We developed multi-component water phantom and could demonstrate the SPGR signal variations to B0 inhomogeneity on an MRI simulator using our multi-component water fraction phantom.

Impact: Our multi-component phantom derived from electron microscopic analysis may be useful to evaluate the differences in MWF values between each signal model, e.g., qMT and mcDESPOT.

2039.
12Imaging the relationship of axon diameter and myelination in macaque and human brain
Ting Gong1, Chiara Maffei1, Evan Dann1, Hong-Hsi Lee1, Hansol Lee1, Susie Y. Huang1, Suzanne N. Haber2,3, and Anastasia Yendiki1
1Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, 2Department of Pharmacology and Physiology, University of Rochester, Rochester, NY, United States, 3McLean Hospital, Belmont, MA, United States

Keywords: White Matter, Microstructure

Motivation: Axon diameter and myelination are essential for conduction of action potentials and therefore related to brain function. However, the relationships between them in white matter (WM) across different species are not well understood.

Goal(s): To investigate the relationship between axon diameter and myelination in human and macaque brain WM.

Approach: We estimate axon diameter and myelin water fraction (MWF), and derive fiber g-ratio, using macaque and human brain data acquired on a preclinical scanner.

Results: Microstructure parameters exhibit consistent patterns across WM tracts and species. Regions with smaller axons tend to have higher packing density and MWF; fiber g-ratio is relatively stable.

Impact: The weak correlations between dMRI measures and MWF suggest they can provide complementary information about fiber morphology. The regional variations of these microstructure measures will be baseline for investigating changes in abnormal tissue conditions such as demyelination and axonal loss.

2040.
13Advanced Diffusion Detects Possible Myelin Changes in Alzheimer’s and Huntington’s Mouse Models and Treatment
Andy Liu1, Danielle A Simmons2, Connor Alvarez1, Yi Wang3, Pascal Spincemaille3, Frank M Longo2, Michael Zeineh1, and Marios Georgiadis 1
1Department of Radiology, Stanford University Medical Center, Stanford, CA, United States, 2Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States, 3Department of Radiology, Weill Cornell Medicine, Ithaca, NY, United States

Keywords: White Matter, Diffusion/other diffusion imaging techniques, Myelin, Neurodegeneration

Motivation: Myelin degeneration is implicated in many neurological diseases. Diffusion and susceptibility MRI provide metrics to assess myelin degeneration. 

Goal(s): Treatment can affect myelination in neurodegeneration and diffusion metrics can be used to follow these changes. 

Approach: After detailed registration to the Allen Atlas, we examined key white matter areas (corpus callosum, fornix). 

Results: We observed diffusivity increases and kurtosis/axonal water fraction decreases in AD mice. We also saw an inverse trend in HD mice. Interestingly, this was reversed by treatment and confirmed histologically. 

Impact: We find diffusion changes suggesting myelin loss in Alzheimer’s mice, and inverse changes in Huntington’s mice that are reversed by disease-modifying treatment and confirmed histologically. Advanced diffusion metrics can be useful biomarkers to monitor myelin changes and treatment in neurodegeneration.

2041.
14Cardiorespiratory fitness is associated with cerebral myelin content in aging
Mary Elizabeth Faulkner1, John Laporte1, Zhaoyuan Gong1, Alex Guo1, Jonghyun Bae1, Elango Palchamy1, and Mustapha Bouhrara1
1Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United States

Keywords: White Matter, Relaxometry, Myelin

Motivation: While higher cardiorespiratory fitness (CRF) is recognized as vital for brain health, its specific connection with white matter integrity, especially cerebral myelination, remains unclear.

Goal(s): This study aims to investigate the association between CRF and myelin in cognitively unimpaired adults spanning a wide age range.

Approach: We employed our advanced multicomponent MR relaxometry method to measure myelin water fraction, a direct proxy of myelin content, while CRF was assessed using the maximum rate of oxygen consumption, peak VO2.

Results: Our results indicate that higher peak VO2 is associated with greater myelin content across several white matter structures, particularly among older adults. 

Impact: This work lays the foundation for future investigations to further elucidate the mechanisms underlying the relationship between cardiorespiratory fitness and cerebral myelination, as well as its potential as an interventional target in addressing age-related neurodegeneration, including in Alzheimer’s disease.

2042.
15Exploring Correlations Between Imaging Biomarkers of Macromolecular, Myelin Water, and Myelin Content in the Brain
James Lo1,2, Chun Zheng1, Jiyo S Athertya1, Bhavsimran S Malhi1, Soo Hyun Shin1, Graeme M Bydder1, Jiang Du1,2,3, and Yajun Ma1
1Department of Radiology, University of California San Diego, San Diego, CA, United States, 2Department of Bioengineering, University of California San Diego, San Diego, CA, United States, 3Radiology Service, Veteran Affairs San Diego Healthcare System, San Diego, CA, United States

Keywords: White Matter, White Matter, MMF, MWF, MPF, Myelin

Motivation: Myelin imaging metrics have varying degrees of association with histology but have not yet been correlated with each other. 

Goal(s): To explore correlations between macromolecular protein, myelin water, and non-aqueous myelin content on a 3T clinical scanner.

Approach: Seven healthy volunteers were scanned using an MT-Cones sequence to provide for two-pool MT modeling of macromolecular proton fraction (MMF), a STAIR-STE-Cones sequence to quantify myelin water fraction (MWF), and a STAIR-UTE-Cone to estimate non-aqueous myelin proton fraction (MPF).

Results: Strong, significant correlations were found between these three myelin imaging biomarkers with R values of 0.856, 0.876, and 0.775, respectively

Impact: Strong positive correlations were found between the three imaging biomarkers of macromolecular, myelin water, and non-aqueous myelin components. This may help in understanding the value of these myelin imaging biomarkers in the assessment of neuroinflammatory and neurodegenerative diseases.