Optimal treatment of glioma has been a subject of debate over the last few decades, since maximal resection can improve survival, whereas preservation of functional peritumoral brain tissue minimizes the risk of postoperative neurological deficits. Our preliminary study uses tractography and neural tissue microstructure modeling based on diffusion MRI to quantify progressive axonal degeneration in proximity to frontotemporal glioma. For this, we sample major white matter pathways that traverse peritumoral penumbra at two time points. The results show a pattern of decreased intra-axonal water fraction beyond anatomical MRI abnormalities, which may indicate a tumor invasion of normal-appearing white matter that potentially advocates supratotal resection.

PURPOSE:In diffusion MRI, vasogenic edema manifests as a major fraction of isotropic water that dilutes the anisotropic intra-axonal portion of the signal. Many tractography algorithms mistake vasogenic edema for the white matter boundary and terminate tracking to prevent producing spurious streamlines. As a result, visual representations of fascicles traversing edema are often compromised, limiting the clinical utility of tractography. METHODS:We address this hurdle with ODF-Fingerprinting (ODF-FP)-a dictionary-based fiber reconstruction algorithm that accommodates variability of neural tissue. By adding a regularization term to the ODF-FP matching formula, we counterbalance the drop of diffusion anisotropy in edematous regions to improve white matter fiber identification. In 19 glioma cases with significant peritumoral vasogenic edema, we quantify the volume of the reconstructed white matter tracts immersed in edema, then we use the cortical regions activated during task-based functional MRI as validation for tractography. To assess the potential for clinical translation, we additionally test the performance of ODF-FP on subsampled single-shell diffusion-weighted images, which contemporary clinical scanners can acquire within a few minutes. RESULTS:Our approach produces high volumes of streamlines traversing vasogenic edema and reaches high overlap with the cortical regions activated at task-based fMRI, significantly outperforming common fiber reconstruction methods in the clinically feasible data set. CONCLUSION:ODF-FP proves effective on research and clinical quality dMRI, which offers an opportunity for application in neurosurgery.

Neuronal electrical activity underlies human cognition, yet its direct, noninvasive measurement in the living human brain remains a fundamental challenge. Existing neuroimaging techniques, including EEG, MEG, and fMRI, are limited by trade-offs in sensitivity and spatial or temporal resolution. Here we propose quantum sensing MRI (qsMRI), a noninvasive approach that enables direct detection of neuronal firing-induced magnetic fields using a clinical MRI system. qsMRI exploits endogenous proton (1H) nuclear spins in water molecules as intrinsic quantum sensors and decodes time-resolved phase information from free induction decay (FID) signals to infer neuronal magnetic fields. We validate qsMRI through simulations, phantom experiments, and human studies at rest and during motor tasks, and provide open experimental procedures to facilitate independent rigorous validation. We further present a case study demonstrating potential applications to neurological disorders. qsMRI represents, to our knowledge, the first-in-human application of quantum sensing on a clinical MRI platform and may lay the foundation for a non-BOLD functional imaging modality capable of probing neuronal firing dynamics in both cortical and deep brain regions.

Sodium MRI can measure in vivo sodium concentrations in people with multiple sclerosis, but the extent to which these alterations reflect metabolic dysfunction in the absence of tissue damage or neuroaxonal loss remains uncertain. Increases in total sodium concentration and extracellular sodium concentration are believed to be indicative of tissue disruption and extracellular space expansion. Conversely, increase in intracellular sodium concentration may represent early and transient responses to neuronal insult, preceding overt tissue damage. Here, we explored the relationship between total sodium concentration, intracellular sodium concentration and intracellular sodium volume fraction, which reflects extracellular sodium concentration, against histology-validated microstructural metrics obtained using diffusion MRI. Fifty-two individuals with multiple sclerosis and 26 healthy controls underwent 1H/23Na MRI. Microstructural parameters were derived using Diffusion Basis Spectrum Imaging and Neurite Orientation Dispersion and Density-Imaging models. A progressive worsening in total sodium concentration and intracellular sodium volume fraction was observed from HCs white matter to normal-appearing white matter and further into T2-hyperintense and T1-hypointense lesions. Both total sodium concentration and intracellular sodium volume fraction, but not intracellular sodium concentration, correlated with Neurite Orientation Dispersion and Density Imaging and Diffusion Basis Spectrum Imaging metrics within multiple sclerosis lesions. Our findings confirm the utility of total sodium concentration and extracellular sodium concentration as indicators of extracellular expansion and axonal loss and underscore intracellular sodium concentration as a valuable biomarker for metabolic dysfunction in multiple sclerosis. Using sodium MRI, Cipriano et al. have shown that extracellular sodium concentration, but not intracellular sodium concentration, is associated with tissue damage and neuroaxonal loss in the brain of individuals with multiple sclerosis. Sodium MRI might help understanding in vivo multiple sclerosis pathology by detecting changes that precede visible damage.

PURPOSE:To develop an improved post-processing pipeline for noise-robust accelerated phase-cycled Cartesian Single (SQ) and Triple Quantum (TQ) sodium (23Na) Magnetic Resonance Imaging (MRI) of in vivo human brain at 7 T. THEORY AND METHODS:Our pipeline aims to tackle the challenges of 23Na Multi-Quantum Coherences (MQC) MRI including low Signal-to-Noise Ratio (SNR) and time-consuming Radiofrequency (RF) phase-cycling. Our method combines low-rank k-space denoising for SNR enhancement with Dynamic Mode Decomposition (DMD) to robustly separate SQ and TQ signal components. This separation is crucial for computing the TQ/SQ ratio, a key parameter of 23Na MQC MRI. We validated our pipeline in silico, in vitro and in vivo in healthy volunteers, comparing it with conventional denoising and Fourier transform (FT) methods. Additionally, we assessed its robustness through ablation experiments simulating a corrupted RF phase-cycle step. RESULTS:Our denoising algorithm doubled SNR compared to non-denoised images and enhanced SNR by up to 29% compared to Wavelet denoising. The low-rank approach produced high-quality images even at later echo times, allowing reduced signal averaging. DMD effectively separated the SQ and TQ signals, even with missing RF phase cycle steps, resulting in superior Structural Similarity (SSIM) of 0.89±0.024 and lower Root Mean Squared Error (RMSE) of 0.055±0.008 compared to conventional FT methods (SSIM=0.71±0.061, RMSE=0.144±0.036). This pipeline enabled high-quality 8x8x15mm3 in vivo 23Na MQC MRI, with a reduction in acquisition time from 48 to 10 min at 7 T. CONCLUSION:The proposed pipeline improves robustness in 23Na MQC MRI by exploiting low-rank properties to denoise signals and DMD to effectively separate SQ and TQ signals. This approach ensures high-quality MR images of both SQ and TQ components, even in accelerated and incomplete RF phase-cycling cases.

Direct sodium MRI (23Na-MRI) derives its signal from spin-manipulation of the 23Na nucleus itself and not the more conventional and familiar 1H-MRI. Although present at much lower concentrations in the human body than the 1H nuclei in the water molecule H2O, advances in coil design and pulse sequence development have enabled the feasibility of human in vivo 23Na-MRI. Additionally, 23Na-MRI has the potential to offer nuanced physiologic insights not available to conventional MRI; this feature forms the basis of interest in its development and optimism for its novel clinical utility. 23Na-MRI has the potential to be a useful noninvasive imaging technique to assess biochemical and physiologic cellular changes in tissues, eg, cell integrity and tissue viability. Pathologically, the concentration of total sodium is elevated in tumors relative to normal counterparts due to increased intracellular sodium and/or an increased proportion of extracellular space (reflecting changes in cell morphology and anomalies of homeostasis). Here we review the technological advancements with improved pulse sequences and reconstruction methods that counter the inherent challenges of measuring sodium concentrations in the pediatric brain (in particular, its short-tissue T2 value) and present detailed imaging approaches to quantifying sodium concentrations in the pediatric brain that can be assessed in various CNS pathologies, with the focus on pediatric brain tumors.

Objective. Whole-body positron emission tomography (PET) imaging is often hindered by respiratory motion during acquisition, causing significant degradation in the quality of reconstructed activity images. An additional challenge in PET/CT imaging arises from the respiratory phase mismatch between CT-based attenuation correction and PET acquisition, leading to attenuation artifacts. To address these issues, we propose two new, purely data-driven methods for the joint estimation of activity, attenuation, and motion in respiratory self-gated time-of-flight PET. These methods enable the reconstruction of a single activity image free from motion and attenuation artifacts.Approach. The proposed methods were evaluated using data from the anthropomorphic Wilhelm phantom acquired on a Siemens mCT PET/CT system, as well as three clinical [18F]FDG PET/CT datasets acquired on a GE DMI PET/CT system. Image quality was assessed visually to identify motion and attenuation artifacts. Lesion uptake values were quantitatively compared across reconstructions without motion modeling, with motion modeling but 'static' attenuation correction, and with our proposed methods.Main results. For the Wilhelm phantom, the proposed methods delivered image quality closely matching the reference reconstruction from a static acquisition. The lesion-to-background contrast for a liver dome lesion improved from 2.0 (no motion correction) to 5.2 (using our proposed methods), matching the contrast from the static acquisition (5.2). In contrast, motion modeling with 'static' attenuation correction yielded a lower contrast of 3.5. In patient datasets, the proposed methods successfully reduced motion artifacts in lung and liver lesions and mitigated attenuation artifacts, demonstrating superior lesion to background separation.Significance. Our proposed methods enable the reconstruction of a single, high-quality activity image that is motion-corrected and free from attenuation artifacts, without the need for external hardware.

Sodium magnetic resonance imaging (MRI) is highly sensitive to cellular ionic balance due to tenfold difference in sodium concentration across membranes, actively maintained by the sodium-potassium (Na+-K+) pump. Disruptions in this pump or membrane integrity, as seen in neurological disorders like epilepsy, multiple sclerosis, bipolar disease, and mild traumatic brain injury, lead to increased intracellular sodium. However, this cellular-level alteration is often masked by the dominant extracellular sodium signal, making it challenging to distinguish sodium populations with mono- vs. bi-exponential transverse (T2) decays - especially given the low signal-to-noise ratio (SNR) even at an advanced clinical field of 3 Tesla. Here, we propose a novel technique that leverages intrinsic difference in T2 decays by acquiring single-quantum images at multiple echo times (TEs) and applying voxel-wise matrix inversion for accurate signal separation. Using numerical models, agar phantoms, and human subjects, we achieved high separation accuracy in phantoms (95.8% for mono-T2 and 72.5-80.4% for bi-T2) and demonstrated clinical feasibility in humans. This approach may enable early detection of neurological disorders and early assessment of treatment responses at the cellular level using sodium MRI at 3T.

White matter fiber reconstructions based on seeking local maxima of Orientation Distribution Functions (ODFs) typically fail to identify fibers crossing at narrow angles below 45^∘ . ODF-Fingerprinting (ODF-FP) replaces the ODF maxima localization mechanism with pattern matching, allowing the use of all information stored in ODFs. In this work, we study the ability of ODF-FP to reconstruct fibers crossing at varied angles spanning 10^∘ – 90^∘ in physical diffusion phantoms composed of textile tubes with 0.8 m diameter, approaching the anatomical scale of axons. Our results show that ODF-FP is able to correctly identify 80± 8% of the crossing fibers regardless of the crossing angle and provide the highest average reconstruction accuracy.

Sodium magnetic resonance imaging (MRI) is sensitive and specific to ionic balance of cells owing to 10 fold difference in sodium concentration across membrane actively maintained by sodium potassium (Na+ K+) pump. Disruption of the pump and membrane integrity, as seen in neurological disorders such as epilepsy, multiple sclerosis, bipolar disease, and mild traumatic brain injury, leads to a large increase in intracellular sodium. Such a cellular level alteration is however overshadowed by large signal from extracellular sodium, leaving behind a long standing pursuit to separate signals from sodium exhibiting mono vs biexponential transverse (T2) decay under the inherent constraint of low signal to noise ratio even at advanced clinical field of 3 Tesla. Here we propose a novel technique that exploits intrinsic difference in their T2 decays by simply acquiring single quantum images at multiple echo times (TEs) and performing accurate matrix inversion at voxel. This approach was then investigated using numerical models, agar phantoms and human subjects, showing high accuracy of the separation in phantoms (95.8 percent for monoT2 and 72.5 to 80.4 percent for biT2) and clinical feasibility in humans. Thus, sodium MRI at 3T can now facilitate detection of neurological disorders early at cellular level and response to treatment as well. Keywords. sodium MRI, single quantum MRI, triple quantum MRI, neuroimaging, neurodegeneration

Neuronal firing generates fast action potentials along axon and slow postsynaptic currents at dendrites, which are difficult to detect and locate by scalp EEG and MEG placed above the skull. Here we propose local quantum sensing via endogenous proton ( 1 H) nuclear spins inside firing neurons and detect magnetic fields indued by both action potentials and postsynaptic currents. Computer simulations and human studies showed that the proposed technique has the potential to non-invasively detect and locate neuronal firings in the brain through the acquisitions of FID signal on a 3T MRI scanner with multi-channel array coil.

Purpose: Sodium MRI is challenging because of the low tissue concentration of the 23 Na nucleus and its extremely fast biexponential transverse relaxation rate. In this article, we present an iterative reconstruction framework using dual-echo 23Na data and exploiting anatomical prior information (AGR) from high-resolution, low-noise, 1 H MR images. This framework enables the estimation and modeling of the spatially-varying signal decay due to transverse relaxation during readout (AGRdm), which leads to images of better resolution and reduced noise resulting in improved quantification of the reconstructed 23Na images. Methods: The proposed framework was evaluated using reconstructions of 30 noise realizations of realistic simulations of dual echo twisted projection imaging (TPI) 23 Na data. Moreover, three dual echo 23 Na TPI brain data sets of healthy controls acquired on a 3T Siemens Prisma system were reconstructed using conventional reconstruction, AGR and AGRdm. Results: Our simulations show that compared to conventional reconstructions, AGR and AGRdm show improved bias-noise characteristics in several regions of the brain. Moreover, AGR and AGRdm images show more anatomical detail and less noise in the reconstructions of the experimental data sets. Compared to AGR and the conventional reconstruction, AGRdm shows higher contrast in the sodium concentration ratio between gray and white matter and between gray matter and the brain stem. Conclusion: AGR and AGRdm generate 23 Na images with high resolution, high levels of anatomical detail, and low levels of noise, potentially enabling high-quality 23 Na MR imaging at 3T.

We reconstruct mouse optic pathways with ODF-Fingerprinting in a challenging crossing area of the optic chiasm. Our method replaces the commonly used peak finding approach with pattern matching when reconstructing white matter fiber directions from orientation distribution functions. As reference, we perform analogous reconstructions using Radial Diffusion Spectrum Imaging and Generalized Q-space Imaging. To obtain ground truth information, we inject intravitreally a 0.1M solution of manganese chloride into four C57BL/6N mice. The optic pathways reconstructed with deterministic tractography based on directional information calculated with our approach reach higher agreement with the ground truth than the other two methods.

Ziel/Aim In PET-MR based motion correction, artifacts in the MR data may lead to impaired estimation of the motion, which may in turn impact a subsequent motion correction of PET data.

PurposeThe accuracy of diffusion MRI tractography reconstruction decreases in the white matter regions with crossing fibers. The optic pathways in rodents provide a challenging structure to test new diffusion tractography approaches because of the small crossing volume within the optic chiasm and the unbalanced 9:1 proportion between the contra- and ipsilateral neural projections from the retina to the lateral geniculate nucleus, respectively.MethodsCommon approaches based on Orientation Distribution Function (ODF) peak finding or statistical inference were compared qualitatively and quantitatively to ODF Fingerprinting (ODF-FP) for reconstruction of crossing fibers within the optic chiasm using in vivo diffusion MRI (n=18$$ n=18 $$ healthy C57BL/6 mice). Manganese-Enhanced MRI (MEMRI) was obtained after intravitreal injection of manganese chloride and used as a reference standard for the optic pathway anatomy.ResultsODF-FP outperformed by over 100% all the tested methods in terms of the ratios between the contra- and ipsilateral segments of the reconstructed optic pathways as well as the spatial overlap between tractography and MEMRI.ConclusionIn this challenging model system, ODF-Fingerprinting reduced uncertainty of diffusion tractography for complex structural formations of fiber bundles.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

BACKGROUND AND PURPOSE:Conventionally, early treatment response to stereotactic radiotherapy in intracranial tumors is often determined by structural MR imaging. Tissue sodium concentration is altered by cellular integrity and energy status in cells. In this study, we aimed to investigate the feasibility of sodium MR imaging at 7T for the preliminary evaluation of radiotherapeutic efficacy for intracranial tumors. MATERIALS AND METHODS:Data were collected from 16 patients (12 men and 4 women, 24-75 years of age) with 22 intracranial tumors who were treated with stereotactic radiation therapy using CyberKnife at our institution between December 1, 2016, and August 15, 2019. Sodium MR imaging was performed at 7T before and 48 hours, 1 week, and 1 month after CyberKnife radiation therapy. Tissue sodium concentration (TSC) was calculated and analyzed based on manually labeled regions of tumors. RESULTS:Ultra-high-field sodium MR imaging clearly showed the intratumoral signal, which is significantly higher than that of normal tissue (t = 5.250, P <.001)., but the edema zone has some influence. The average TSC ratios of tumor to CSF in the 22 tumors, contralateral normal tissues, edema zones, frontal cortex, and frontal white matter were 0.66 (range, 0.23-1.5), 0.30 (range, 0.15-0.43), 0.58 (range, 0.25-1.21), 0.25 (range, 0.17-0.42), and 0.30 (range, 0.19-0.49), respectively. A total of 12 tumors in 8 patients were scanned at 48 hours, 1 week, and 1 month after treatment. The average TSC at 48 hours after treatment was 0.06 higher than that before treatment and began to decrease at 1 week. The TSC ratios of 10 continued to decline and 2 tumors increased at 1 month, respectively. Tumor volume decreased by 2.4%-99% after 3 months. CONCLUSIONS:Changes in the TSC can be quantified by sodium MR imaging at 7T and used to detect radiobiologic alterations in intracranial tumors at early time points after CyberKnife radiation therapy.

Purpose Orientation Distribution Function (ODF) peak finding methods typically fail to reconstruct fibers crossing at shallow angles below 40°, leading to errors in tractography. ODF‐Fingerprinting (ODF‐FP) with the biophysical multicompartment diffusion model allows for breaking this barrier. Methods A randomized mechanism to generate a multidimensional ODF‐dictionary that covers biologically plausible ranges of intra‐ and extra‐axonal diffusivities and fraction volumes is introduced. This enables ODF‐FP to address the high variability of brain tissue. The performance of the proposed approach is evaluated on both numerical simulations and a reconstruction of major fascicles from high‐ and low‐resolution in vivo diffusion images. Results ODF‐FP with the suggested modifications correctly identifies fibers crossing at angles as shallow as 10 degrees in the simulated data. In vivo, our approach reaches 56% of true positives in determining fiber directions, resulting in visibly more accurate reconstruction of pyramidal tracts, arcuate fasciculus, and optic radiations than the state‐of‐the‐art techniques. Moreover, the estimated diffusivity values and fraction volumes in corpus callosum conform with the values reported in the literature. Conclusion The modified ODF‐FP outperforms commonly used fiber reconstruction methods at shallow angles, which improves deterministic tractography outcomes of major fascicles. In addition, the proposed approach allows for linearization of the microstructure parameters fitting problem.