C-MORPH

Cell specific morphology in neurodegeneration and inflammation

Funded by: ERC
Grant Size: EUR 1,500,000

C MORPH Billede 1

Brain structure determines function. Disentangling regional microstructural properties and understanding how these properties constitute brain function is a central goal of neuroimaging of the human brain and a key prerequisite for a mechanistic understanding of brain diseases and their treatment. Previous studies using magnetic resonance (MR) imaging have established links between regional brain microstructure and inter- individual variation in brain function, but this line of research has been limited by the non-specificity of MR-derived markers. This hampers the application of MR imaging as a tool to identify specific fingerprints of the underlying disease process.

In this project, we advance methodology on state-of-the-art MR hardware and harvest the synergy of these methods to realize Cell-specific in vivo MORPHometry (C-MORPH) of the intact human brain and spinal cord. In focus is the hybrid of advanced diffusion encoding strategies, spectroscopy and novel imaging approaches.

C MORPH Billede 2

Our aim is to establish methods and analyses to derive cell-type specific tissue properties in the healthy and diseased brain. In particular, we aim for isolating the severity of specific pathological processes and their development over time. To date, such processes are more or less superimposed in conventional clinical imaging data. Once validated, the experimental methods and analyses will be simplified and adapted to provide clinically applicable tools. This will push the frontiers of MR-based personalized medicine, guiding therapeutic decisions by providing sensitive probes of cell-specific microstructural changes caused by inflammation, neurodegeneration or treatment response.

The C-MORPH project was initiated in the end of 2018 with the ERC Staring Grant awarded to the P.I. Henrik Lundell.

C MORPH Billede 3

Associated Publications

Samo Lasič, …, Henrik Lundell (2025)
Spectral Principal Axis System (SPAS) and tuning of tensor-valued encoding for microscopic anisotropy and time-dependent diffusion in the rat brain,
Imaging Neuroscience 3: IMAG.a.35.

M Jokivuolle, …, H Lundell (2025)
Assessing tumor microstructure with time-dependent diffusion imaging: Considerations and feasibility on clinical MRI and MRI-Linac,
Medical Physics 52(1):346-361.

S Lasič, ..., H Lundell et al (2024)
Tuned exchange imaging: Can the filter exchange imaging pulse sequence be adapted for applications with thin slices and restricted diffusion?
NMR in Biomedicine 37 (11), e5208.

H Lundell and C Steele (2024)
Cerebellar imaging with diffusion magnetic resonance imaging: approaches, challenges, and potential.
Current Opinion in Behavioral Sciences 56, 101353.

Lasič S, … Lundell H (2022)
Stay on the beat with tensor-valued encoding: time-dependent diffusion and cell size estimation in ex vivo heart,
Frontiers in Physics 2022:812115.

Lundell H, Najac C, Bulk M, Kan HE, Webb A G, Ronen I (2021)
Compartmental diffusion and microstructural properties of human brain gray and white matter studied with double diffusion encoding magnetic resonance spectroscopy of metabolites and wate,
Neuroimage, 234:117981.

Lundell, H.; Ingo, C.; Dyrby, T.B.; Ronen, I.
Cytosolic diffusivity and microscopic anisotropy of N-acetyl aspartate in human white matter with diffusion-weighted MRS at 7T.
Analytical Science Journals, 31 March 2020.https://doi.org/10.1002/nbm.4304

Rafael N. Henriques, Marco Palombo, Sune N. Jespersen, Noam Shemesh, Henrik Lundell, Andrada Ianuş.
Double diffusion encoding and applications for biomedical imaging. 2020.
Journal of Neuroscience Methods. https://doi.org/10.1016/j.jneumeth.2020.108989

Lundell, Nilsson, Dyrby, et al,
Multidimensional diffusion MRI with spectrally modulated gradients reveals unprecedented microstructural detail, 2019
Scientific Reports 9 (1), 9026

Lundell, Christensen, Bornsen, et al,
Serum and cerebrospinal fluid neurofilament levels predict longitudinal atrophy of the cervical spinal cord in progressive MS, 2019
MULTIPLE SCLEROSIS JOURNAL 25, p. 469

Lundell, Webb, Ronen,
Cell specific anisotropy with double diffusion encoding spectroscopy in the human brain at 7T, 2018. in proc.
ISMRM 2018, 26, p. 259

Lundell, Nilsson, Westin, Topgaard, and Lasič,
Spectral anisotropy in multidimensional diffusion encoding, 2018. in proc.
ISMRM 2018, 26, p. 887

Boer, V. O., Ronen, I., Pedersen, J., Petersen, E. T. & Lundell, H.
Metabolite diffusion weighted imaging with golden angle radial echo planar spectroscopic imaging.
ISMRM 27th Annual Meeting & Exhibition 2019.
| WebSearch |

Lasic, S., Lundell, H. & Topgaard, D.
The tuned trinity of b-tensors.
ISMRM 27th Annual Meeting & Exhibition 2019.
| WebSearch |

Lundell, H., Nilsson, M., Szczepankiewicz, F., Westin, C-F., Topgaard, D. & Lasic, S.
Reducing spectral anisotropy in isotropic b-tensor multidimensional diffusion encoding.
ISMRM 27th Annual Meeting & Exhibition 2019.
| WebSearch |

Najac, C., Lundell, H., Bulk, M., Kan, H. E., Webb, A. G. & Ronen, I.
Estimating compartment- and cell-specific microscopic anisotropy in the human brain using double-diffusion encoding spectroscopy at 7T.
ISMRM 27th Annual Meeting & Exhibition 2019.
| WebSearch |

Szczepankiewicz, F., Lasic, S., Nilsson, M., Lundell, H., Westin, C-F. & Topgaard, D.
Is spherical diffusion encoding rotation invariant? An investigation of diffusion time-dependence in the healthy brain.
ISMRM 27th Annual Meeting & Exhibition 2019.
| WebSearch |

Dyrby, T. B., Innocenti, G., Bech, M. & Lundell, H.
Validation strategies for the interpretation of microstructure imaging using diffusion MRI.
NeuroImage. 182, p. 62-79, 2018.
| WebSearch |

DRCMR Members

Henrik Lundell

Kristin Engel