Sune Nørhøj Jespersen

• M.Sc., PhD (Sc.), DMSc
• Professor at Aarhus University

Evaluating tissue microstructure and membrane integrity in the living human brain through diffusion water exchange imaging is challenging due to requirements for a high signal-to-noise ratio and short diffusion times dictated by relatively fast exchange processes. The goal of this work was to demonstrate the feasibility of in vivo imaging of tissue...

Glioblastomas are aggressive brain tumors with dismal prognosis. One of the main bottlenecks for developing more effective therapies for glioblastoma stems from their histologic and molecular heterogeneity, leading to distinct tumor microenvironments and disease phenotypes. Effectively characterizing these features would improve the clinical manage...

Magnetic susceptibility MRI offers potential insights into the chemical composition and microstructural organization of tissue. However, estimating magnetic susceptibility in white matter is challenging due to anisotropic subvoxel Larmor frequency shifts caused by axonal microstructure relative to the B0 field orientation. Recent biophysical models...

Glioblastomas are aggressive brain tumors with dismal prognosis. One of the main bottlenecks for developing more effective therapies for glioblastoma stems from their histologic and molecular heterogeneity, leading to distinct tumor microenvironments and disease phenotypes. Effectively characterizing these features would improve the clinical manage...

Purpose The purpose of this study is to develop a method for selecting uniform wave vectors for double diffusion encoding (DDE) to improve the accuracy and reliability of diffusion measurements. Methods The method relies on identifying orthogonal wave vectors with rotations, and representing these rotations as points on a three‐dimensional sphere...

Evaluating tissue microstructure and membrane integrity in the living human brain through diffusion-water exchange imaging is challenging due to requirements for a high signal-to-noise ratio and short diffusion times dictated by relatively fast exchange processes. The goal of this work was to demonstrate the feasibility of in vivo imaging of tissue...

Background and purpose Diffusion tensor imaging (DTI) has been proposed to guide the anisotropic expansion from gross tumor volume to clinical target volume (CTV), aiming to integrate known tumor spread patterns into the CTV. This study investigate the potential of using a DTI atlas as an alternative to patient-specific DTI for generating anisotrop...

Glioblastomas are aggressive brain tumors with dismal prognosis. One of the main bottlenecks for developing more effective therapies for glioblastoma stems from their histologic and molecular heterogeneity, leading to distinct tumor microenvironments and disease phenotypes. Effectively characterizing these features would improve the clinical manage...

Glioblastomas are aggressive brain tumors with dismal prognosis. One of the main bottlenecks for developing more effective therapies for glioblastoma stems from their histologic and molecular heterogeneity, leading to distinct tumor microenvironments and disease phenotypes. Effectively characterizing these features would improve the clinical manage...

This study aims to validate if MRI can measure anisotropic mesoscopic Larmor frequency shifts from white matter axonal microstructure relative to the B0 direction and if dMRI can estimate this anisotropy. Recent models describe how mesoscopic Larmor frequency shifts depend on induced magnetic fields by axons, described by an orientation distributio...

Glioblastomas are aggressive brain tumors with dismal prognosis. One of the main bottlenecks for developing more effective therapies for glioblastoma stems from their histologic and molecular heterogeneity, leading to distinct tumor microenvironments and disease phenotypes. Effectively characterizing these features would improve the clinical manage...

Motivation: This study assesses the Neurite Exchange Imaging (NEXI) microstructure model in human cortex using clinical MRI data, addressing the model's clinical applicability. Goal(s): How meaningful, robust, and reproducible are microstructural properties in the human cortex estimated using the NEXI diffusion model on clinical data? Approach: S...

We present a model of the Larmor frequency shift in white matter (WM) that includes myelinated axons with arbitrary orientation dispersion, microscopic WM susceptibility anisotropy, and spherical inclusions with scalar susceptibility to represent iron and other sources. We validate our analytical results with computer simulations and investigate th...

Introduction Approximately one-third of all persons with multiple sclerosis (pwMS) are older, i.e., having an age ≥60 years. Whilst ageing and MS separately elicit deteriorating effects on brain morphology, neuromuscular function, and physical function, the combination of ageing and MS may pose a particular challenge. To counteract such detrimental...

Marčenko-Pastur PCA (MPPCA) denoising is emerging as an effective means for noise suppression in MR imaging (MRI) acquisitions with redundant dimensions. However, MPPCA performance can be severely compromised by spatially correlated noise—an issue typically affecting most modern MRI acquisitions—almost to the point of returning the original images...

Magnetic susceptibility imaging may provide valuable information about chemical composition and microstructural organization of tissue. However, its estimation from the MRI signal phase is particularly difficult as it is sensitive to magnetic tissue properties ranging from the molecular to macroscopic scale. The MRI Larmor frequency shift measured...

Purpose To extend quantitative susceptibility mapping to account for microstructure of white matter (WM) and demonstrate its effect on ex vivo mouse brain at 16.4T. Theory and Methods Previous studies have shown that the MRI measured Larmor frequency also depends on local magnetic microstructure at the mesoscopic scale. Here, we include effects fr...

Purpose X‐nuclei (also called non‐proton MRI) MRI and spectroscopy are limited by the intrinsic low SNR as compared to conventional proton imaging. Clinical translation of x‐nuclei examination warrants the need of a robust and versatile tool improving image quality for diagnostic use. In this work, we compare a novel denoising method with fewer inp...

MP-PCA denoising has become the method of choice for denoising MRI data since it provides an objective threshold to separate the signal components from unwanted thermal noise components. In rodents, thermal noise in the coils is an important source of noise that can reduce the accuracy of activation mapping in fMRI. Further confounding this problem...

Purpose Estimating magnetic susceptibility using MRI depends on inverting a forward relationship between the susceptibility and measured Larmor frequency. However, an often‐overlooked constraint in susceptibility fitting is that the Larmor frequency is only measured inside the sample, and after successful background field removal, susceptibility so...

Marčenko-Pastur (MP) PCA denoising is emerging as an effective means for noise suppression in MRI acquisitions with redundant dimensions. However, MP-PCA performance is severely compromised by spatially correlated noise — an issue typically affecting most modern MRI acquisitions — almost to the point of returning the original images with little or...

MP-PCA denoising has become the method of choice for denoising in MRI since it provides an objective threshold to separate the desired signal from unwanted thermal noise components. In rodents, thermal noise in the coils is an important source of noise that can reduce the accuracy of activation mapping in fMRI. Further confounding this problem, ven...

Purpose To develop a denoising strategy leveraging redundancy in high‐dimensional data. Theory and Methods The SNR fundamentally limits the information accessible by MRI. This limitation has been addressed by a host of denoising techniques, recently including the so‐called MPPCA: principal component analysis of the signal followed by automated ran...

Magnetic susceptibility of tissue can provide valuable information about its chemical composition and microstructural organization. However, the relation between the magnetic microstructure and the measurable Larmor frequency shift is only understood for a few idealized cases. Here we analyze the microstructure formed by magnetized, NMR‐invisible i...

Accurate estimation of microscopic magnetic field variations induced in biological tissue can be valuable for mapping tissue composition in health and disease. Here, we present an extension to Quantitative susceptibility mapping (QSM) to account for local white matter (WM) magnetic microstructure by using our previously presented model for solid cy...

Estimating magnetic susceptibility using MRI depends on inverting a forward relationship between the susceptibility and measured Larmor frequency. However, an often-overlooked constraint in susceptibility fitting is that the Larmor frequency is only measured inside the sample, and after background field removal, susceptibility sources should only r...

The signal to noise ratio (SNR) fundamentally limits the information accessible by magnetic resonance imaging (MRI). This limitation has been addressed by a host of denoising techniques, recently including so-called MPPCA: Principal component analysis (PCA) of the signal followed by automated rank estimation, exploiting the Marchenko-Pastur (MP) di...

We present a theoretical framework for the NMR and MRI measured Larmor frequency in media with magnetized microstructure using the mesoscopic Lorentz sphere and the principle of coarse graining. We obtain an analytical expression for infinite cylinders with arbitrary orientation dispersion and show how it depends on the fiber orientation distributi...

Characterizing neural tissue microstructure is a critical goal for future neuroimaging. Diffusion MRI (dMRI) provides contrasts that reflect diffusing spins’ interactions with myriad microstructural features of biological systems. However, the specificity of dMRI remains limited due to the ambiguity of its signals vis-à-vis the underlying microstru...

Noninvasively detecting and characterizing modulations in cellular scale micro-architecture remains a desideratum for contemporary neuroimaging. Diffusion MRI (dMRI) has become the mainstay methodology for probing microstructure, and, in ischemia, its contrasts have revolutionized stroke management. Diffusion kurtosis imaging (DKI) has been shown t...

Diffusion MRI (dMRI) provides contrast that reflect diffusing spins' interactions with microstructural features of biological systems, but its specificity remains limited due to the ambiguity of its relation to the underlying microstructure. To improve specificity, biophysical models of white matter (WM) typically express dMRI signals according to...

Purpose The impact of microscopic diffusional kurtosis (µK), arising from restricted diffusion and/or structural disorder, remains a controversial issue in contemporary diffusion MRI (dMRI). Recently, correlation tensor imaging (CTI) was introduced to disentangle the sources contributing to diffusional kurtosis, without relying on a‐priori multi‐ga...

Despite the clear importance of language in our life, our vital ability to quickly and effectively learn new words and meanings is neurobiologically poorly understood. Conventional knowledge maintains that language learning—especially in adulthood—is slow and laborious. Furthermore, its structural basis remains unclear. Even though behavioural mani...

Purpose The general utility of diffusion kurtosis imaging (DKI) is challenged by its poor robustness to imaging artifacts and thermal noise that often lead to implausible kurtosis values. Theory and Methods A robust scalar kurtosis index can be estimated from powder‐averaged diffusion‐weighted data. We introduce a novel DKI estimator that uses thi...

Purpose: The impact of microscopic diffusional kurtosis ($\mu K$) - arising from restricted diffusion and/or structural disorder - remains a controversial issue in contemporary diffusion MRI (dMRI). Recently, Correlation Tensor MRI (CTI) was introduced to disentangle the sources contributing to diffusional kurtosis, without relying on a-priori assu...

Noninvasively detecting and characterizing modulations in cellular scale micro-architecture is a desideratum for contemporary neuroimaging. Diffusion MRI (dMRI) has become the mainstay methodology for probing microstructure, and, in ischemia, its contrasts have revolutionized stroke management. However, the sources of the contrasts observed in conv...

Background Mean kurtosis (MK), one of the parameters derived from diffusion kurtosis imaging (DKI), has shown increased sensitivity to tissue microstructure damage in several neurological disorders. Methods Thirty-seven patients with relapsing-remitting MS and eleven healthy controls (HC) received brain imaging on a 3T MR scanner, including a fast...

Information about tissue on the microscopic and mesoscopic scales can be accessed by modelling diffusion MRI signals, with the aim of extracting microstructure-specific biomarkers. The standard model (SM) of diffusion, currently the most broadly adopted microstructural model, describes diffusion in white matter (WM) tissues by two Gaussian componen...

A recent randomized controlled trial in young patients with long‐term post‐concussion symptoms showed that a novel behavioral intervention “Get going After concussIoN” is superior to enhanced usual care in terms of symptom reduction. It is unknown whether these interventional effects are associated with microstructural brain changes. The aim of thi...

Diffusion Magnetic Resonance Imaging (dMRI) is one of the most important contemporary non-invasive modalities for probing tissue structure at the microscopic scale. The majority of dMRI techniques employ standard single diffusion encoding (SDE) measurements, covering different sequence parameter ranges depending on the complexity of the method. Alt...

Diffusion Magnetic Resonance Imaging (dMRI) is one of the most important contemporary non-invasive modalities for probing tissue structure at the microscopic scale. The majority of dMRI techniques employ standard single diffusion encoding (SDE) measurements, covering different sequence parameter ranges depending on the complexity of the method. Alt...

To study axonal microstructure with diffusion MRI, axons are typically modeled as straight impermeable cylinders, whereby the transverse diffusion MRI signal can be made sensitive to the cylinder’s inner diameter. However, the shape of a real axon varies along the axon direction, which couples the longitudinal and transverse diffusion of the overal...

To study axonal microstructure with diffusion MRI, axons are typically modeled as straight impermeable cylinders, whereby the transverse diffusion MRI signal can be made sensitive to the cylinder's inner diameter. However, the shape of a real axon varies along the axon direction, which couples the longitudinal and transverse diffusion of the overal...

Diffusional Kurtosis Magnetic Resonance Imaging (DKI) quantifies the extent of non-Gaussian water diffusion, which has been shown to be a very sensitive biomarker for microstructure in health and disease. However, DKI is not specific to any microstructural property per se since kurtosis may emerge from several different sources. Q-space trajectory...

Diffusion kurtosis imaging (DKI), is an imaging modality that yields novel disease biomarkers and in combination with nervous tissue modeling, provides access to microstructural parameters. Recently, DKI and subsequent estimation of microstructural model parameters has been used for assessment of tissue changes in neurodegenerative diseases and ass...

Computational models of biophysical tissue properties have been widely used in diffusion MRI (dMRI) research to elucidate the link between microstructural properties and MR signal formation. For brain tissue, the research community has developed the so-called Standard Model (SM) that has been widely used. However, in clinically applicable acquisiti...

Diffusion Kurtosis MRI (DKI) quantifies the degree of non-Gaussian water diffusion -a sensitive biomarker for microstructure in health and disease. However, DKI is not specific to any microstructural property per se since kurtosis might emerge from different sources. Q-space trajectory encoding schemes have been proposed to decouple kurtosis relate...

Computational models of biophysical tissue properties have been widely used in diffusion MRI (dMRI) research to elucidate the link between microstructural properties and MR signal formation. For brain tissue, the research community has developed the so-called Standard Model (SM) that has been widely used. However, in clinically applicable acquisiti...

Computational models of biophysical tissue properties have been widely used in diffusion MRI (dMRI) research to elucidate the link between microstructural properties and MR signal formation. For brain tissue, the research community has developed the so-called Standard Model (SM) that has been widely used. However, in clinically applicable acquisiti...

Repetitive mild traumatic brain injuries are linked to the neurodegenerative and neuropsychiatric disorders, however, often diagnosed as normal under conventional neuroimaging techniques. We employed multiparametric MRI (Diffusion MRI, Perfusion MRI and 1H MRS of the ipsilateral cerebral cortex) to probe microstructural, pathophysiological and meta...

Repetitive mild traumatic brain injury (mTBI) has long term health effects and may result in the development of neurodegenerative or neuropsychiatric disorders. Histology shows axonal and dendritic beading, synaptic atrophy, vasodilation and gliosis occuring within hours/days post-mTBI. However, current neuroimaging techniques are unable to detect...

FIGURE S1 The ex vivo mouse brain raw data and standard DTI FA maps: A.1, b‐value = 0 map displaying the WM and GM regions used to plot the signal decays in panels A.2 and A.3; A.2, raw signal decays for different SDE gradient directions and for WM and GM regions of interest; A.3, raw powder‐averaged signal decays for parallel and perpendicular DDE...

Purpose: Microscopic fractional anisotropy ({\mu}FA) can disentangle microstructural information from orientation dispersion. While double diffusion encoding (DDE) MRI methods are widely used to extract accurate {\mu}FA, it has only recently been proposed that powder-averaged single diffusion encoding (SDE) signals, when coupled with the diffusion...

PURPOSE: Multi-exponential relaxometry is a powerful tool for characterizing tissue, but generally requires high image signal-to-noise ratio (SNR). This work evaluates the use of principal-component-analysis (PCA) denoising to mitigate these SNR demands and improve the precision of relaxometry measures. METHODS: PCA denoising was evaluated using bo...

Purpose Biophysical tissue models are increasingly used in the interpretation of diffusion MRI (dMRI) data, with the potential to provide specific biomarkers of brain microstructural changes. However, it has been shown recently that, in the general Standard Model, parameter estimation from dMRI data is ill‐conditioned even when very high b‐values a...

Designing novel diffusion-weighted pulse sequences to probe tissue microstructure beyond the conventional Stejskal-Tanner family is currently of broad interest. One such technique, multidimensional diffusion MRI, has been recently proposed to afford model-free decomposition of diffusion signal kurtosis into terms originating from either ensemble va...

Purpose Multi‐exponential relaxometry is a powerful tool for characterizing tissue, but generally requires high image signal‐to‐noise ratio (SNR). This work evaluates the use of principal‐component‐analysis (PCA) denoising to mitigate these SNR demands and improve the precision of relaxometry measures. Methods PCA denoising was evaluated using bot...

Purpose Microscopic fractional anisotropy (µFA) can disentangle microstructural information from orientation dispersion. While double diffusion encoding (DDE) MRI methods are widely used to extract accurate µFA, it has only recently been proposed that powder‐averaged single diffusion encoding (SDE) signals, when coupled with the diffusion standard...

Depression is a leading cause of disability worldwide and it can often ensue after a prolonged exposure to mild stressors. Despite intensive preclinical and clinical research, an objective test to diagnose the depression is still not available, causing suboptimal diagnosis and treatment. Recently, neuronal tracing technique and stereology showed pe...

Diffusion kurtosis imaging (DKI), is an imaging modality that yields novel disease biomarkers and provides access to microstructural parameters. DKI and subsequent estimation of microstructural model parameters has been commonly used for assessment of tissue changes in neurodegenerative diseases and the animal models of such diseases. In this study...

Purpose: Biophysical tissue models are increasingly used in the interpretation of diffusion MRI (dMRI) data, with the potential to provide specific biomarkers of brain microstructural changes. However, the general Standard Model has recently shown that model parameter estimation from dMRI data is ill-posed unless very strong magnetic gradients are...

This article presents longitudinal ¹H-MR Spectroscopy (¹H-MRS) data from ventral hippocampus and in vivo diffusion MRI (dMRI) data of the brain from control and anhedonic rats. The ¹H-MRS and dMRI data were acquired using a 9.4 T preclinical imaging system. Before MRI experiments, animals were exposed to unpredictable chronic mild stress exposure f...

Chronic mild stress (CMS) exposure of animals induces anhedonia, one of the core symptoms of depression. The underlying mechanism of depression is still not clear, however, dendritic atrophy in the hippocampus (HP) and prefrontal cortex (PFC) associate with cognitive impairment, while dendritic hypertrophy in the amygdala (AM) is linked to anxiety....

Diffusion kurtosis imaging (DKI) is a new promising MRI technique with microstructural sensitivity superior to conventional diffusion tensor (DTI) based methods. In stroke, considerable mismatch exists between the infarct lesion outline obtained from the two methods, kurtosis and diffusion tensor derived metrics. We aim to investigate if this misma...

Table A. Data of the whole brain volumes. Table B. Data of the infarct volumes. Table C. Data of the re-analyzed infarct volumes. (XLSX)

As part of an issue celebrating 2 decades of Joseph Ackerman editing the Journal of Magnetic Resonance, this paper reviews recent progress in one of the many areas in which Ackerman and his lab has made significant contributions: NMR measurement of diffusion in biological media, specifically in brain tissue. NMR diffusion signals display exquisite...

Neurovascular coupling mechanisms give rise to vasodilation and functional hyperemia upon neural activation, thereby altering blood oxygenation. This blood oxygenation level dependent (BOLD) contrast allows studies of activation patterns in the working human brain by functional MRI (fMRI). The BOLD-weighted fMRI signal shows characteristic transien...

Mapping tissue microstructure with MRI holds great promise as a noninvasive window into tissue organization at the cellular level. Having originated within the realm of diffusion NMR in the late 1970s, this field is experiencing an exponential growth in the number of publications. At the same time, model-based approaches are also increasingly incor...

Chronic mild stress leads to depression in many cases and is linked to several debilitating diseases including mental disorders. Recently, neuronal tracing techniques, stereology, and immunohistochemistry have revealed persistent and significant microstructural alterations in the hippocampus, hypothalamus, prefrontal cortex, and amygdala, which for...

(a) Mean kurtosis (MK), (b) Axial kurtosis (AK) and (c) Radial kurtosis (RK) data as mean ± confidence interval (CI) from MC, VC, AC and SC regions of the brain from control, anhedonic and resilient group. Linear mixed model regression analysis was performed in Matlab. No significant alteration was observed in any ROIs of the stress group with all...

Dendritic density % data as mean ± confidence interval from MC, VC, AC and SC regions of the brain from control, anhedonic and resilient group. No significant alteration was observed in any region of the stress groups in comparison to control. (TIF)

Average effect size (ES) and confidence interval (CI) of axonal density (%), dendritic density (%), and cortical thickness form MC, SC, AC, and VC region of the brain from control, anhedonic, and resilient group. (XLSX)

Designing novel diffusion-weighted NMR and MRI pulse sequences aiming to probe tissue microstructure with techniques extending beyond the conventional Stejskal-Tanner family is currently of broad interest. One such technique, multidimensional diffusion MRI, has been recently proposed to afford model-free decomposition of diffusion signal kurtosis i...

Microscopic diffusion anisotropy ({\mu}A) has been recently gaining increasing attention for its ability to decouple the average compartment anisotropy from orientation dispersion. Advanced diffusion MRI sequences, such as double diffusion encoding (DDE) and double oscillating diffusion encoding (DODE) have been used for mapping {\mu}A. However, th...

Microscopic diffusion anisotropy ({\mu}A) has been recently gaining increasing attention for its ability to decouple the average compartment anisotropy from orientation dispersion. Advanced diffusion MRI sequences, such as double diffusion encoding (DDE) and double oscillating diffusion encoding (DODE) have been used for mapping {\mu}A. However, th...

Primary objectives: We hypothesized that the microstructure of the corpus callosum, thalamus and hippocampus, as measured with diffusion and Mean of the Kurtosis Tensor (MKT) MRI, differs between healthy subjects and patients with extensive and minimal post-concussion symptoms (PCS) and that MKT measures correlate with PCS severity and self-reporte...

Chronic mild stress (CMS) induced depression elicits several debilitating symptoms and causes a significant economic burden on society. High variability in the symptomatology of depression poses substantial impediment to accurate diagnosis and therapy outcome. CMS exposure induces significant metabolic and microstructural alterations in the hippoca...

Diffusion kurtosis imaging (DKI) is an extension of the popular diffusion tensor imaging (DTI) technique. DKI takes into account leading deviations from Gaussian diffusion stemming from a number of effects related to the microarchitecture and compartmentalization in biological tissues. DKI therefore offers increased sensitivity to subtle microstruc...

Diffusion kurtosis imaging (DKI) is an extension of diffusion tensor imaging that accounts for leading non-Gaussian diffusion effects. In DKI studies, a wide range of different gradient strengths (b-values) is used, which is known to affect the estimated diffusivity and kurtosis parameters. Hence there is a need to assess the accuracy and precision...

Cerebral ischemia causes widespread capillary no-flow in animal studies. The extent of microvascular impairment in human stroke, however, is unclear. We examined how acute intra-voxel transit time characteristics and subsequent recanalization affect tissue outcome on follow-up MRI in a historic cohort of 126 acute ischemic stroke patients. Based on...

Biophysical modelling of diffusion MRI is necessary to provide specific microstructural tissue properties. However, estimating model parameters from data with limited diffusion gradient strength, such as clinical scanners, has proven unreliable due to a shallow optimization landscape. On the other hand, estimation of diffusion kurtosis (DKI) parame...

Biophysical modelling of diffusion MRI is necessary to provide specific microstructural tissue properties. However, estimating model parameters from data with limited diffusion gradient strength, such as clinical scanners, has proven unreliable due to a shallow optimization landscape. On the other hand, estimation of diffusion kurtosis (DKI) parame...

The striatum and thalamus are subcortical structures intimately involved in addiction. The morphology and microstructure of these have been studied in murine models of cocaine addiction (CA), showing an effect of drug use, but also chronological age in morphology. Human studies using non-invasive magnetic resonance imaging (MRI) have shown inconsis...