arXiv subjects

Linda Knutsson

Publications and source records attributed to Linda Knutsson.

3 recordsLinked to original sources

arXiv2026

Characterising Water Exchange in Gliomas Using Diffusion MRI with Free Gradient Waveforms

Transmembrane water permeability, which regulates cellular water exchange and is influenced by water channels such as aquaporin-4 (AQP4), has been implicated in glioma progression and may affect tumour infiltration and treatment response. Non-invasive mapping of water exchange may therefore provide biomarkers of glioma pathology. This study investigates the feasibility of characterizing water exchange in gliomas using diffusion MRI with free gradient waveforms, known as the Restriction-Exchange (ResEx) approach, which enables exchange quantification independent of restricted diffusion effects. Thirteen patients with histologically confirmed gliomas (ten glioblastomas, three astrocytomas) underwent preoperative MRI at 3T using a custom ResEx protocol. Multiple diffusion-weighted acquisitions with selective exchange sensitivity were performed to estimate voxel-wise maps of the apparent diffusion coefficient (ADC), diffusion kurtosis, and water exchange rate. ResEx-derived maps revealed heterogeneous spatial patterns across and within tumours. Elevated exchange rates were commonly observed in enhancing tumour margins, potentially reflecting smaller cells, increased membrane permeability or AQP4 upregulation. In some cases, elevated exchange extended into non-enhancing peritumoural regions. Exchange values in oedema were slightly higher than in healthy tissue, suggesting potential infiltration or membrane disruption. Diffusion MRI with free gradient waveforms permits non-invasive mapping of water exchange in gliomas and reveals physiological information not captured by standard imaging. Exchange rate mapping may offer novel biomarkers of tumour aggressiveness, infiltration, and treatment response, and holds promise for surgical and radiotherapy planning.

physics.med-ph↗

arXiv2024

Dynamic Glucose Enhanced Imaging using Direct Water Saturation

Purpose: Dynamic glucose enhanced (DGE) MRI studies employ chemical exchange saturation transfer (CEST) or spin lock (CESL) to study glucose uptake. Currently, these methods are hampered by low effect size and sensitivity to motion. To overcome this, we propose to utilize exchange-based linewidth (LW) broadening of the direct water saturation (DS) curve of the water saturation spectrum (Z-spectrum) during and after glucose infusion (DS-DGE MRI). Methods: To estimate the glucose-infusion-induced LW changes ($\Delta$LW), Bloch-McConnell simulations were performed for normoglycemia and hyperglycemia in blood, gray matter (GM), white matter (WM), CSF, and malignant tumor tissue. Whole-brain DS-DGE imaging was implemented at 3 tesla using dynamic Z-spectral acquisitions (1.2 s per offset frequency, 38 s per spectrum) and assessed on four brain tumor patients using infusion of 35 g of D-glucose. To assess $\Delta$LW, a deep learning-based Lorentzian fitting approach was employed on voxel-based DS spectra acquired before, during, and post-infusion. Area-under-the-curve (AUC) images, obtained from the dynamic $\Delta$LW time curves, were compared qualitatively to perfusion-weighted imaging (PWI). Results: In simulations, $\Delta$LW was 1.3%, 0.30%, 0.29/0.34%, 7.5%, and 13% in arterial blood, venous blood, GM/WM, malignant tumor tissue, and CSF, respectively. In vivo, $\Delta$LW was approximately 1% in GM/WM, 5-20% for different tumor types, and 40% in CSF. The resulting DS-DGE AUC maps clearly outlined lesion areas. Conclusions: DS-DGE MRI is highly promising for assessing D-glucose uptake. Initial results in brain tumor patients show high-quality AUC maps of glucose-induced line broadening and DGE-based lesion enhancement similar and/or complementary to PWI.

physics.med-ph↗

arXiv2021

Probing restricted diffusion and exchange using free gradient waveforms: validation by numerical simulations

Monitoring time-dependence with diffusion MRI yields observables sensitive to compartment sizes (restricted diffusion) and membrane permeability (water exchange). However, restricted diffusion and exchange have opposite effects on the diffusion-weighted signal, which can confound parameter estimates. In this work, we present a signal representation that captures the effects of both restricted diffusion and exchange up to second order in b-value and is compatible with gradient waveforms of arbitrary shape. The representation features mappings from a gradient waveform to two scalars that separately control the sensitivity to restriction and exchange. We demonstrate that these scalars span a two-dimensional space that can be used to choose waveforms that selectively probe restricted diffusion or exchange, in order to eliminate the correlation between the two phenomena. We found that waveforms with specific but unconventional shapes provide an advantage over conventional pulsed and oscillating gradient acquisitions. We also show that parametrisation of waveforms into a two-dimensional space can be used to understand protocols from other approaches that probe restricted diffusion and exchange. For example, we find that the variation of mixing time in filter-exchange imaging corresponds to variation of our exchange-weighting scalar at a fixed value of the restriction-weighting scalar. Numerical evaluation of the proposed signal representation using Monte Carlo simulations on a synthetic substrate showed that the theory is applicable to sizes in the range 2 - 7 micrometres and barrier-limited exchange in the range 0 - 20 s$^{-1}$. The presented theory constitutes a simple and intuitive description of how restricted diffusion and exchange influence the signal as well as how to design a protocol to separate the two effects.

physics.med-ph↗