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Ordinola, A., Abramian, D., Herberthson, M., Eklund, A. & Özarslan, E. (2025). Super-resolution mapping of anisotropic tissue structure with diffusion MRI and deep learning. Scientific Reports, 15(1), Article ID 6580.
Open this publication in new window or tab >>Super-resolution mapping of anisotropic tissue structure with diffusion MRI and deep learning
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2025 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 15, no 1, article id 6580Article in journal (Refereed) Published
Abstract [en]

Diffusion magnetic resonance imaging (diffusion MRI) is widely employed to probe the diffusive motion of water molecules within the tissue. Numerous diseases and processes affecting the central nervous system can be detected and monitored via diffusion MRI thanks to its sensitivity to microstructural alterations in tissue. The latter has prompted interest in quantitative mapping of the microstructural parameters, such as the fiber orientation distribution function (fODF), which is instrumental for noninvasively mapping the underlying axonal fiber tracts in white matter through a procedure known as tractography. However, such applications demand repeated acquisitions of MRI volumes with varied experimental parameters demanding long acquisition times and/or limited spatial resolution. In this work, we present a deep-learning-based approach for increasing the spatial resolution of diffusion MRI data in the form of fODFs obtained through constrained spherical deconvolution. The proposed approach is evaluated on high quality data from the Human Connectome Project, and is shown to generate upsampled results with a greater correspondence to ground truth high-resolution data than can be achieved with ordinary spline interpolation methods. Furthermore, we employ a measure based on the earth mover’s distance to assess the accuracy of the upsampled fODFs. At low signal-to-noise ratios, our super-resolution method provides more accurate estimates of the fODF compared to data collected with 8 times smaller voxel volume.

Keywords
Diffusion MRI, super resolution, deep learning, brain, white matter
National Category
Radiology and Medical Imaging Medical Imaging
Identifiers
urn:nbn:se:liu:diva-211968 (URN)10.1038/s41598-025-90972-7 (DOI)001433275500049 ()39994322 (PubMedID)2-s2.0-85218687239 (Scopus ID)
Funder
Linköpings universitetVinnova, 2021-01954
Note

Funding Agencies|Linkping University [2021-01954]; ITEA/VINNOVA project ASSIST (Automation)

Available from: 2025-03-01 Created: 2025-03-01 Last updated: 2025-05-17
Witherspoon, V. J., Komlosh, M. E., Benjamini, D., Özarslan, E., Lavrik, N. & Basser, P. J. (2024). Novel pore size-controlled, susceptibility matched, 3D-printed MRI phantoms. Magnetic Resonance in Medicine, 91(6), 2431-2442
Open this publication in new window or tab >>Novel pore size-controlled, susceptibility matched, 3D-printed MRI phantoms
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2024 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 91, no 6, p. 2431-2442Article in journal (Refereed) Published
Abstract [en]

PurposeWe report the design concept and fabrication of MRI phantoms, containing blocks of aligned microcapillaires that can be stacked into larger arrays to construct diameter distribution phantoms or fractured, to create a "powder-averaged" emulsion of randomly oriented blocks for vetting or calibrating advanced MRI methods, that is, diffusion tensor imaging, AxCaliber MRI, MAP-MRI, and multiple pulsed field gradient or double diffusion-encoded microstructure imaging methods. The goal was to create a susceptibility-matched microscopically anisotropic but macroscopically isotropic phantom with a ground truth diameter that could be used to vet advanced diffusion methods for diameter determination in fibrous tissues.MethodsTwo-photon polymerization, a novel three-dimensional printing method is used to fabricate blocks of capillaries. Double diffusion encoding methods were employed and analyzed to estimate the expected MRI diameter.ResultsSusceptibility-matched microcapillary blocks or modules that can be assembled into large-scale MRI phantoms have been fabricated and measured using advanced diffusion methods, resulting in microscopic anisotropy and random orientation.ConclusionThis phantom can vet and calibrate various advanced MRI methods and multiple pulsed field gradient or diffusion-encoded microstructure imaging methods. We demonstrated that two double diffusion encoding methods underestimated the ground truth diameter.

Place, publisher, year, edition, pages
WILEY, 2024
Keywords
anisotropic phantom; DDE; diameter; DTI; random orientation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-201311 (URN)10.1002/mrm.30029 (DOI)001163861900001 ()38368618 (PubMedID)2-s2.0-85185671523 (Scopus ID)
Note

Funding Agencies|Intramural Research Program; National Institute of Child Health and Human Development; Center for Neuroscience and Regenerative Medicine; National Institute of General Medical Sciences; [K99GM140338-01]

Available from: 2024-03-05 Created: 2024-03-05 Last updated: 2025-03-13Bibliographically approved
Boito, D., Herberthson, M., Dela Haije, T., Blystad, I. & Özarslan, E. (2023). Diffusivity-limited q-space trajectory imaging. Magnetic Resonance Letters, 3(2), 187-196
Open this publication in new window or tab >>Diffusivity-limited q-space trajectory imaging
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2023 (English)In: Magnetic Resonance Letters, ISSN 2772-5162, Vol. 3, no 2, p. 187-196Article in journal (Refereed) Published
Abstract [en]

Q-space trajectory imaging (QTI) allows non-invasive estimation of microstructural features of heterogeneous porous media via diffusion magnetic resonance imaging performed with generalised gradient waveforms. A recently proposed constrained estimation framework, called QTI+, improved QTI’s resilience to noise and data sparsity, thus increasing the reliability of the method by enforcing relevant positivity constraints. In this work we consider expanding the set of constraints to be applied during the fitting of the QTI model. We show that the additional conditions, which introduce an upper bound on the diffusivity values, further improve the retrieved parameters on a publicly available human brain dataset as well as on data acquired from healthy volunteers using a scanner-ready protocol.

Place, publisher, year, edition, pages
KeAi Publishing Communications, 2023
Keywords
Diffusion; Diffusion MRI; q-space trajectory imaging; QTI; Microstructure; Microscopic anisotropy; QTI+Constrained
National Category
Medical Engineering Mathematics
Identifiers
urn:nbn:se:liu:diva-198025 (URN)10.1016/j.mrl.2022.12.003 (DOI)001223797500001 ()
Funder
Swedish Foundation for Strategic ResearchVinnova
Note

Funding agencies: This research was funded by Sweden’s Innovation Agency (VINNOVA) ASSIST, Analytic Imaging Diagnostic Arena (AIDA), Swedish Foundation for Strategic Research (RMX18-0056), Linköping University Center for Industrial Information Technology (CENIIT), LiU Cancer Barncancerfonden, and a research grant (00028384) from VILLUM FONDEN.

Available from: 2023-09-22 Created: 2023-09-22 Last updated: 2024-11-15Bibliographically approved
Boito, D., Eklund, A., Tisell, A., Levi, R., Özarslan, E. & Blystad, I. (2023). MRI with generalized diffusion encoding reveals damaged white matter in patients previously hospitalized for COVID-19 and with persisting symptoms at follow-up. Brain Communications, 5(6), Article ID fcad284.
Open this publication in new window or tab >>MRI with generalized diffusion encoding reveals damaged white matter in patients previously hospitalized for COVID-19 and with persisting symptoms at follow-up
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2023 (English)In: Brain Communications, E-ISSN 2632-1297, Vol. 5, no 6, article id fcad284Article in journal (Refereed) Published
Abstract [en]

There is mounting evidence of the long-term effects of COVID-19 on the central nervous system, with patients experiencing diverse symptoms, often suggesting brain involvement. Conventional brain MRI of these patients shows unspecific patterns, with no clear connection of the symptomatology to brain tissue abnormalities, whereas diffusion tensor studies and volumetric analyses detect measurable changes in the brain after COVID-19. Diffusion MRI exploits the random motion of water molecules to achieve unique sensitivity to structures at the microscopic level, and new sequences employing generalized diffusion encoding provide structural information which are sensitive to intravoxel features. In this observational study, a total of 32 persons were investigated: 16 patients previously hospitalized for COVID-19 with persisting symptoms of post-COVID condition (mean age 60 years: range 41–79, all male) at 7-month follow-up and 16 matched controls, not previously hospitalized for COVID-19, with no post-COVID symptoms (mean age 58 years, range 46–69, 11 males). Standard MRI and generalized diffusion encoding MRI were employed to examine the brain white matter of the subjects. To detect possible group differences, several tissue microstructure descriptors obtainable with the employed diffusion sequence, the fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, microscopic anisotropy, orientational coherence (Cc) and variance in compartment’s size (CMD) were analysed using the tract-based spatial statistics framework. The tract-based spatial statistics analysis showed widespread statistically significant differences (P < 0.05, corrected for multiple comparisons using the familywise error rate) in all the considered metrics in the white matter of the patients compared to the controls. Fractional anisotropy, microscopic anisotropy and Cc were lower in the patient group, while axial diffusivity, radial diffusivity, mean diffusivity and CMD were higher. Significant changes in fractional anisotropy, microscopic anisotropy and CMD affected approximately half of the analysed white matter voxels located across all brain lobes, while changes in Cc were mainly found in the occipital parts of the brain. Given the predominant alteration in microscopic anisotropy compared to Cc, the observed changes in diffusion anisotropy are mostly due to loss of local anisotropy, possibly connected to axonal damage, rather than white matter fibre coherence disruption. The increase in radial diffusivity is indicative of demyelination, while the changes in mean diffusivity and CMD are compatible with vasogenic oedema. In summary, these widespread alterations of white matter microstructure are indicative of vasogenic oedema, demyelination and axonal damage. These changes might be a contributing factor to the diversity of central nervous system symptoms that many patients experience after COVID-19.

Place, publisher, year, edition, pages
Oxford University Press, 2023
Keywords
MRI; Q-space trajectory imaging; microscopic fractional anisotropy; fractional anisotropy; COVID-19
National Category
Radiology, Nuclear Medicine and Medical Imaging Neurosciences Medical Imaging
Identifiers
urn:nbn:se:liu:diva-199215 (URN)10.1093/braincomms/fcad284 (DOI)001103246200003 ()37953843 (PubMedID)
Funder
Vinnova, 2021-01954Wallenberg Foundations
Note

Funding: Analytic Imaging Diagnostic Arena (AIDA), a Medtech4Health initiative; ITEA/ VINNOVA (The Swedish Innovation Agency) project ASSIST (Automation, Surgery Support and Intuitive 3D visualization to optimize workflow in IGT SysTems) [2021-01954]; Wallenberg Center for Molecular Medicine

Available from: 2023-11-19 Created: 2023-11-19 Last updated: 2025-02-09Bibliographically approved
Ordinola, A., Cai, S., Lundberg, P., Bai, R. & Özarslan, E. (2023). On the sampling strategies and models for measuring diffusion exchange with a double diffusion encoding sequence. Magnetic Resonance Letters, 3, 232-247
Open this publication in new window or tab >>On the sampling strategies and models for measuring diffusion exchange with a double diffusion encoding sequence
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2023 (English)In: Magnetic Resonance Letters, ISSN 2772-5162, Vol. 3, p. 232-247Article in journal (Refereed) Published
Abstract [en]

Water exchange between the different compartments of a heterogeneous specimen can be characterized via diffusion magnetic resonance imaging (dMRI). Many analysis frameworks using dMRI data have been proposed to describe exchange, often using a double diffusion encoding (DDE) stimulated echo sequence. Techniques such as diffusion exchange weighted imaging (DEWI) and the filter exchange and rapid exchange models, use a specific subset of the full space DDE signal. In this work, a general representation of the DDE signal was employed with different sampling schemes (namely constant �1, diagonal and anti-diagonal) from the data reduction models to estimate exchange. A near-uniform sampling scheme was proposed and compared with the other sampling schemes. The filter exchange and rapid exchange models were also applied to estimate exchange with their own subsampling schemes. These subsampling schemes and models were compared on both simulated data and experimental data acquired with a benchtop MR scanner. In synthetic data, the diagonal and near-uniform sampling schemes performed the best due to the consistency of their estimates with the ground truth. In experimental data, the shifted diagonal and near-uniform sampling schemes outperformed the others, yielding the most consistent estimates with the full space estimation. The results suggest the feasibility of measuring exchange using a general representation of the DDE signal along with variable sampling schemes. In future studies, algorithms could be further developed for the optimization of sampling schemes, as well as incorporating additional properties, such as geometry and diffusion anisotropy, into exchange frameworks.

Place, publisher, year, edition, pages
KeAi Publishing Communications, 2023
Keywords
Diffusion MRI; Water exchange; Sampling schemes; Double diffusion encoding
National Category
Medical Engineering
Identifiers
urn:nbn:se:liu:diva-198024 (URN)10.1016/j.mrl.2023.05.003 (DOI)001222151400001 ()
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)Swedish Research Council
Note

Funding agencies:This research was funded by the Swedish Foundation for International Cooperation in Research and Higher Education (STINT), and the Swedish Research Council (Dnr 2022–04715).

Available from: 2023-09-22 Created: 2023-09-22 Last updated: 2024-05-31Bibliographically approved
Richie-Halford, A., Cieslak, M., Ai, L., Caffarra, S., Covitz, S., Franco, A. R., . . . Rokem, A. (2022). An analysis-ready and quality controlled resource for pediatric brain white-matter research. Scientific Data, 9(1)
Open this publication in new window or tab >>An analysis-ready and quality controlled resource for pediatric brain white-matter research
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2022 (English)In: Scientific Data, E-ISSN 2052-4463, Vol. 9, no 1Article in journal (Refereed) Published
Abstract [en]

We created a set of resources to enable research based on openly-available diffusion MRI (dMRI) data from the Healthy Brain Network (HBN) study. First, we curated the HBN dMRI data (N?=?2747) into the Brain Imaging Data Structure and preprocessed it according to best-practices, including denoising and correcting for motion effects, susceptibility-related distortions, and eddy currents. Preprocessed, analysis-ready data was made openly available. Data quality plays a key role in the analysis of dMRI. To optimize QC and scale it to this large dataset, we trained a neural network through the combination of a small data subset scored by experts and a larger set scored by community scientists. The network performs QC highly concordant with that of experts on a held out set (ROC-AUC?=?0.947). A further analysis of the neural network demonstrates that it relies on image features with relevance to QC. Altogether, this work both delivers resources to advance transdiagnostic research in brain connectivity and pediatric mental health, and establishes a novel paradigm for automated QC of large datasets.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-189363 (URN)10.1038/s41597-022-01695-7 (DOI)000866490900002 ()36224186 (PubMedID)
Available from: 2022-10-19 Created: 2022-10-19 Last updated: 2023-10-02Bibliographically approved
Afzali, M., Pieciak, T., Jones, D. K., Schneider, J. E. & Özarslan, E. (2022). Cumulant expansion with localization: A new representation of the diffusion MRI signal. Frontiers in Neuroimaging, 1
Open this publication in new window or tab >>Cumulant expansion with localization: A new representation of the diffusion MRI signal
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2022 (English)In: Frontiers in Neuroimaging, E-ISSN 2813-1193, Vol. 1Article in journal (Refereed) Published
Abstract [en]

Diffusion MR is sensitive to the microstructural features of a sample. Fine-scale characteristics can be probed by employing strong diffusion gradients while the low b-value regime is determined by the cumulants of the distribution of particle displacements. A signal representation based on the cumulants, however, suffers from a finite convergence radius and cannot represent the ‘localization regime' characterized by a stretched exponential decay that emerges at large gradient strengths. Here, we propose a new representation for the diffusion MR signal. Our method provides not only a robust estimate of the first three cumulants but also a meaningful extrapolation of the entire signal decay.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2022
Keywords
diusion MRI, cumulant expansion, localization regime, kurtosis, gradient strength
National Category
Signal Processing
Identifiers
urn:nbn:se:liu:diva-198026 (URN)10.3389/fnimg.2022.958680 (DOI)001537149200001 ()37555138 (PubMedID)2-s2.0-105005547189 (Scopus ID)
Funder
Wellcome trust, 096646/Z/11/ZWellcome trust, 219536/Z/19/ZSwedish Foundation for Strategic Research
Note

Funding agencies: This research was funded in whole, or in part, by a Wellcome Trust Investigator Award (219536/Z/19/Z, 096646/Z/11/Z) and a Wellcome Trust Strategic Award (104943/Z/14/Z), the Swedish Foundation for Strategic Research (RMX18-0056), Linköping University Center for Industrial Information Technology (CENIIT), Sweden's Innovation Agency (VINNOVA) ASSIST, and Analytic Imaging Diagnostic Arena (AIDA). This work was also supported by the British Heart Foundation, UK (SI/14/1/30718), EPSRC (EP/M029778/1), and The Wolfson Foundation. TP acknowledges the Polish National Agency for Academic Exchange for the grant PPN/BEK/2019/1/00421 under the Bekker programme and the Ministry of Science and Higher Education (Poland) under the scholarship for outstanding young scientists (692/STYP/13/2018).

Available from: 2023-09-22 Created: 2023-09-22 Last updated: 2025-10-10
Özarslan, E., Schultz, T., Zhang, E. & Fuster, A. (Eds.). (2021). Anisotropy across fields and scales. Cham: Springer
Open this publication in new window or tab >>Anisotropy across fields and scales
2021 (English)Collection (editor) (Refereed)
Place, publisher, year, edition, pages
Cham: Springer, 2021. p. 280
Series
Mathematics and Visualization, ISSN 1612-3786, E-ISSN 2197-666X
Keywords
tensor; tensor fields; higher-order harmonics; spherical harmonics; visualization; image processing; medical imaging; diffusion-weighted imaging (DWI); structural mechanics; astrophysics; statistics; open access
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-173659 (URN)10.1007/978-3-030-56215-1 (DOI)9783030562144 (ISBN)9783030562151 (ISBN)
Available from: 2021-03-01 Created: 2021-03-01 Last updated: 2021-09-16Bibliographically approved
Yolcu, C., Herberthson, M., Westin, C.-F. & Özarslan, E. (2021). Magnetic resonance assessment of effective confinement anisotropy with orientationally-averaged single and double diffusion encoding. In: Evren Özarslan,Thomas Schultz, Eugene Zhang, Andrea Fuster (Ed.), Anisotropy across fields and scales: (pp. 203-223). Springer
Open this publication in new window or tab >>Magnetic resonance assessment of effective confinement anisotropy with orientationally-averaged single and double diffusion encoding
2021 (English)In: Anisotropy across fields and scales / [ed] Evren Özarslan,Thomas Schultz, Eugene Zhang, Andrea Fuster, Springer, 2021, p. 203-223Chapter in book (Refereed)
Abstract [en]

Porous or biological materials comprise a multitude of micro-domainscontaining water. Diffusion-weighted magnetic resonance measurements are sensitive to the anisotropy of the thermal motion of such water. This anisotropy can bedue to the domain shape, as well as the (lack of) dispersion in their orientations.Averaging over measurements that span all orientations is a trick to suppress thelatter, thereby untangling it from the influence of the domains’ anisotropy on thesignal. Here, we consider domains whose anisotropy is modeled as being the resultof a Hookean (spring) force, which has the advantage of having a Gaussian diffusionpropagator while still confining the spatial range for the diffusing particles. In fact,this confinement model is the effective model of restricted diffusion when diffusion isencoded via gradients of long durations, making the model relevant to a broad rangeof studies aiming to characterize porous media with microscopic subdomains. In thisstudy, analytical expressions for the powder-averaged signal under this assumptionare given for so-called single and double diffusion encoding schemes, which sensitize the MR signal to the diffusive displacement of particles in, respectively, one ortwo consecutive time intervals. The signal for one-dimensional diffusion is shownto exhibit power-law dependence on the gradient strength while its coefficient bearssignatures of restricted diffusion.

Place, publisher, year, edition, pages
Springer, 2021
Series
Mathematics and Visualization, ISSN 1612-3786, E-ISSN 2197-666X
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-173660 (URN)10.1007/978-3-030-56215-1_10 (DOI)9783030562144 (ISBN)9783030562151 (ISBN)
Note

Funding agencies: : Swedish Foundation for Strategic Research AM13-0090, the Swedish Research Council 2016-04482, Linköping University Center for Industrial Information Technology (CENIIT), VINNOVA/ITEA3 17021 IMPACT, and National Institutes of Health P41EB015902 and R01MH074794. 

Available from: 2021-03-01 Created: 2021-03-01 Last updated: 2024-01-10Bibliographically approved
Herberthson, M., Özarslan, E. & Westin, C.-F. (2021). Variance measures for symmetric positive (semi) definite tensors in two dimensions. In: Evren Özarslan,Thomas Schultz, Eugene Zhang, Andrea Fuster (Ed.), Anisotropy across fields and scales: (pp. 3-22). Cham: Springer
Open this publication in new window or tab >>Variance measures for symmetric positive (semi) definite tensors in two dimensions
2021 (English)In: Anisotropy across fields and scales / [ed] Evren Özarslan,Thomas Schultz, Eugene Zhang, Andrea Fuster, Cham: Springer, 2021, p. 3-22Chapter in book (Refereed)
Place, publisher, year, edition, pages
Cham: Springer, 2021
Series
Mathematics and Visualization, ISSN 1612-3786, E-ISSN 2197-666X
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-173663 (URN)10.1007/978-3-030-56215-1_1 (DOI)9783030562144 (ISBN)9783030562151 (ISBN)
Note

Funding agencies: Swedish Foundation for Strategic Research AM13-0090, the Swedish Research Council 2016-04482, Linköping University Center for Industrial Information Technology (CENIIT), VINNOVA/ITEA3 17021 IMPACT, and National Institutes of Health P41EB015902 and R01MH074794.

Available from: 2021-03-01 Created: 2021-03-01 Last updated: 2024-01-10Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-0859-1311

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