Noam Shemesh

Fundação Champalimaud · Champalimaud Neuroscience Programme

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...

Understanding the dynamics of stability/plasticity balances during adulthood is pivotal for learning, disease, and recovery from injury. However, the brain-wide topography of sensory remapping remains unknown. Here, using a first-of-its-kind setup for delivering patterned visual stimuli in a rodent magnetic resonance imaging (MRI) scanner, coupled...

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...

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...

Spontaneous fluctuations in functional magnetic resonance imaging (fMRI) signals correlate across distant brain areas, shaping functionally relevant intrinsic networks. However, the generative mechanism of fMRI signal correlations, and in particular the link with locally-detected ultra-slow oscillations, are not fully understood. To investigate thi...

Temporal Diffusion Ratio (TDR) is a recently proposed dMRI technique (Dell'Acqua et al., proc. ISMRM 2019) which provides contrast between areas with restricted diffusion and areas either without restricted diffusion or with length scales too small for characterisation. Hence, it has a potential for informing on pore sizes, in particular the presen...

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...

The continuity illusion occurs when visual stimuli are presented at a sufficiently high frequency, thereby triggering a shift from the static to the dynamic vision mode. This facilitates perception of continuous and moving objects, which is key for interactions with the surrounding environment. However, how the continuity illusion is encoded along...

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...

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...

The value of preclinical diffusion MRI (dMRI) is substantial. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages including higher signal-to-noise ratio and spatial resolution compared to in...

The value of in vivo preclinical diffusion MRI (dMRI) is substantial. Small-animal dMRI has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. Many of the influential works in this field were first performed in small animals or ex vivo samples. The steps from...

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...

Temporal Diffusion Ratio (TDR) is a recently proposed dMRI technique (Dell’Acqua, 2019) which provides contrast between areas with restricted diffusion and areas either without restricted diffusion or with length scales too small for characterisation. Hence, it has a potential for mapping pore sizes, in particular large axon diameters or other cell...

Multiple myeloma (MM), the third most frequent hematological cancer worldwide, is characterized by the proliferation of neoplastic plasma cells in the bone marrow (BM). One of the hallmarks of MM is a permissive BM microenvironment. Increasing evidence suggests that cell-to-cell communication between myeloma and immune cells via tumor cell-derived...

Understanding the dynamics of stability/plasticity balances during adulthood and how they are sculpted by sensory experience is pivotal for learning, disease, and recovery from injury. Although invasive recordings suggest that sensory experience promotes single-cell and population-level plasticity in adults, the brain-wide topography of sensory rem...

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows comparison with invasive or terminal procedures. To date, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. We introduce Sta...

The Correlation Tensor MRI (CTI) framework has been recently formulated to disentangle anisotropic, isotropic, and microscopic kurtosis sources without a priori assumptions from Double-Diffusion-Encoding (DDE) data. In this work, group average maps (templates) are presented for the first time, thereby mapping the contrasts for anisotropic and isotr...

Parkinson’s disease (PD) is associated with irreparable damage to dopaminergic neurons in brain areas involved in movement. Frequently, a very early symptom of PD involves an impaired sense of smell, while other studies suggest a broader impairment of other sensory modalities. Still, the associated brain-wide mechanisms underlying this phenomenon r...

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these pati...

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...

Purpose: Enhanced cell proliferation in tumors can be associated with altered metabolic profiles and dramatic microenvironmental changes. Downfield magnetic resonance spectroscopy (MRS) has received increasing attention due to its ability to report on labile resonances of molecules not easily detected in upfield 1 H MRS. Image-selected-in-vivo-spe...

Diffusion MRI (dMRI) provides unique insights into the neural tissue milieu by probing interactions between diffusing molecules and tissue microstructure. Most dMRI techniques focus on white matter (WM) tissues, nevertheless, interest in gray matter characterisations is growing. The Soma and Neurite Density MRI (SANDI) methodology harnesses a model...

Diffusion MRI (dMRI) has become one of the most important imaging modalities for noninvasively probing tissue microstructure. Diffusional Kurtosis MRI (DKI) quantifies the degree of non-gaussian diffusion, which in turn has been shown to increase sensitivity towards, e.g., disease and orientation mapping in neural tissue. However, the specificity o...

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...

The fundamental principles driving spontaneous long-range correlations between distant brain areas - known as intrinsic functional connectivity - remain unclear. To investigate this, we develop an ultrafast functional Magnetic Resonance Imaging (fMRI) approach with unprecedented temporal resolution (38 milliseconds) in the rat brain. We detect a re...

Objectives Glioblastoma multiforme (GBM), the most aggressive glial brain tumors, can metabolize glucose through glycolysis and mitochondrial oxidation pathways. While specific dependencies on those pathways are increasingly associated with treatment response, detecting such GBM subtypes in vivo remains elusive. Here, we develop a dynamic glucose-e...

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...

The basal ganglia (BG) are a group of subcortical nuclei responsible for motor and executive function. Central to BG function are striatal cells expressing D1 (D1R) and D2 (D2R) dopamine receptors. D1R and D2R cells are considered functional antagonists that facilitate voluntary movements and inhibit competing motor patterns, respectively. However,...

Diffusion MRI (dMRI) has become one of the most important imaging modalities for noninvasively probing tissue microstructure. Diffusion Kurtosis MRI (DKI) quantifies the degree of non-gaussian diffusion, which in turn has been shown to increase sensitivity towards, e.g. , disease and orientation mappings in neural tissue. However, the specificity o...

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...

Diffusion MRI (dMRI) provides unique insights into the neural tissue milieu by probing interaction of diffusing molecules and tissue microstructure. Most dMRI techniques focus on white matter tissues (WM) due to the relatively simpler modelling of diffusion in the more organized tracts; however, interest is growing in gray matter characterisations....

Diffusion MRI (dMRI) has become an invaluable tool to assess the microstructural organization of brain tissue. Depending on the specific acquisition settings, the dMRI signal encodes specific properties of the underlying diffusion process. In the last two decades, several signal representations have been proposed to fit the dMRI signal and decode s...

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...

Purpose Bowel motion is a significant source of artifacts in mouse abdominal MRI. Fasting and administration of hyoscine butylbromide (BUSC) have been proposed for bowel motion reduction but with inconsistent results and limited efficacy assessments. Here, we evaluate these regimes for mouse abdominal MRI at high field. Methods Thirty‐two adult C5...

Resolving the underlying sources of kurtosis in biological systems is emerging as a promising strategy for non-invasive quantitative characterization of tissue microstructure. Recently, a novel framework termed Correlation Tensor Imaging (CTI), based on double-diffusion-encoding MRI, was shown to disentangle anisotropic, isotropic, and microscopic...

The basal ganglia (BG) are a group of subcortical nuclei responsible for motor control, motor learning and executive function. Central to BG function are striatal medium spiny neurons (MSNs) expressing D1 and D2 dopamine receptors. D1 and D2 MSNs are typically considered functional antagonists that facilitate voluntary movements and inhibit competi...

Diffusion MRI (dMRI) has become an invaluable tool to assess the microstructural organization of brain tissue. Depending on the specific acquisition settings, the dMRI signal encodes specific properties of the underlying diffusion process. In the last two decades, several signal representations have been proposed to fit the dMRI signal and decode s...

Functional magnetic resonance spectroscopy (fMRS) quantifies metabolic variations upon presentation of a stimulus and can therefore provide complementary information compared to activity inferred from functional magnetic resonance imaging (fMRI). Improving the temporal resolution of fMRS can be beneficial to clinical applications where detailed inf...

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...

Functional Magnetic Resonance Imaging (fMRI) has transformed our understanding of brain function in-vivo. However, the neurovascular coupling mechanisms underlying fMRI are somewhat “distant” from neural activity. Interestingly, evidence from Intrinsic Optical Signals (IOSs) indicates that neural activity is also coupled to (sub)cellular morphologi...

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...

Detecting neuroplasticity in global brain circuits in vivo is key for understanding myriad processes such as memory, learning, and recovery from injury. Functional Magnetic Resonance Imaging (fMRI) is instrumental for such in vivo mappings, yet it typically relies on mapping changes in spatial extent of activation or via signal amplitude modulation...

Diffusion tensor imaging (DTI) is a well-established technique for mapping brain microstructure and white matter tracts in vivo . High resolution DTI, however, is usually associated with low intrinsic sensitivity and therefore long acquisition times. By increasing sensitivity, high magnetic fields can alleviate these demands, yet high fields are al...

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...

Purpose: Bowel motion is a source of artifacts in mouse abdominal MRI. The use of fasting and hyoscine butylbromide (BUSC) for the purpose of bowel motion reduction has been inconsistently reported, without a thorough assessment of efficacy. This work aimed to better evaluate these methods in the mouse with high-field MRI. Methods: Thirty-two adult...

Behaviour involves complex dynamic interactions across many brain regions. Detecting whole-brain activity in mice performing sophisticated behavioural tasks could facilitate insights into distributed processing underlying behaviour, guide local targeting, and help bridge the disparate spatial scales between rodent and human studies. Here, we presen...

This work introduces a compartment-based model for apparent cell body (namely soma) and neurite density imaging (SANDI) using non-invasive diffusion-weighted MRI (DW-MRI). The existing conjecture in brain microstructure imaging through DW-MRI presents water diffusion in white (WM) and grey (GM) matter as restricted diffusion in neurites, modelled b...

Axon caliber plays a crucial role in determining conduction velocity and, consequently, in the timing and synchronization of neural activation. Noninvasive measurement of axon radii could have significant impact on the understanding of healthy and diseased neural processes. Until now, accurate axon radius mapping has eluded in vivo neuroimaging, ma...

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...

Functional Magnetic Resonance Imaging (fMRI) is predominantly harnessed for spatially mapping activation foci along distributed pathways. However, resolving dynamic information on activation sequence remains elusive. Here, we show an ultra-fast fMRI (ufMRI) approach - a facilitating non-invasive methodology for mapping Blood-Oxygenation-Level-Depen...

Functional magnetic resonance spectroscopy (fMRS) quantifies metabolic variations upon presentation of a stimulus and can therefore provide complementary information compared to functional magnetic resonance imaging (fMRI). However, to our knowledge, fMRS has not yet been performed in the mouse, despite that murine models are crucial for basic and...

Chemical Exchange Saturation Transfer (CEST) Magnetic Resonance Imaging (MRI) is a molecular imaging methodology capable of mapping brain metabolites with relatively high spatial resolution. Specificity is the main goal of such experiments; yet CEST is confounded by spectral overlap between different molecular species. Here, we overcome this major...

Functional Magnetic Resonance Imaging (fMRI) has transformed our understanding of brain function in-vivo. However, the neurovascular coupling mechanisms underlying fMRI are somewhat "distant" from neural activity. Interestingly, evidence from Intrinsic Optical Signals (IOSs) indicates that neural activity is also coupled to (sub)cellular morphologi...

Complexity on the micron scale is an essential aspect of most biological systems. In many cases, microarchitectural features underpin proper tissue function, while aberrations on the micron scale are typically correlated with significant loss of function. Imaging microstructural features in vivo can thus play an important role in understanding basi...

Purpose: Mesorectal lymph node staging plays an important role in treatment decision making. Here, we explore the benefit of higher-order diffusion MRI models accounting for non-Gaussian diffusion effects to classify mesorectal lymph nodes both 1) ex vivo at ultrahigh field correlated with histology and 2) in vivo in a clinical scanner upon patient...