Gray, Erin M.

Abstract White matter bundles play a crucial role in cognitive functions by rapidly transmitting information between brain regions. Inter-areal conduction guides the integration of information and conduction velocity is a fundamental parameter in theories and models of brain function. However, distributions of conduction velocity remain difficult to characterize in vivo in humans. In this work, we integrated diffusion magnetic resonance imaging (dMRI) tractography with intracranial electrical stimulation during clinical stereo-electroencephalography (sEEG) monitoring in 17 subjects to measure conduction velocity within four major white matter bundles. Our findings reveal that human brain conduction is characterized by high variability both within and between bundles, reflecting a predominance of slow connections alongside rare high-speed connections. Because conduction velocity in myelinated fibers follows an approximately linear relationship with axon diameter, we derive underlying axon diameter distributions and show that these estimates are comparable to previous post-mortem studies. These findings demonstrate a heavily skewed distribution of human neural conduction velocities and show that structural heterogeneity shapes the timing and integration of information in large-scale networks.

Abstract Hypoxia constrains cerebral oxygen availability and challenges brain function and stability. Although hypoxia-responsive functional connectivity (HR-FC) reorganizes rapidly with declining arterial oxygen partial pressure, its relationship to local neurovascular activity remains unclear. We examined time-resolved amplitude of low-frequency fluctuations (ALFF) in blood-oxygenation-level dependent (BOLD) fMRI during graded acute hypoxia in healthy adults, performing a continuous cognitive test (Go/No-go task) with concurrent physiological monitoring. Dynamic ALFF and functional connectivity were estimated using a sliding-window approach and analyzed across large-scale brain networks defined by Schaefer’s 17-network parcellation. Severe hypoxia elicited temporally dissociated responses across modalities. Functional connectivity increased monotonically, whereas ALFF exhibited pronounced nonlinear modulation, including phase-dependent divergence across networks. During hypoxic decompensation, the default mode network (DefaultA) showed marked ALFF suppression, whereas a ventral secondary somatosensory-dominant network (SomMotB) exhibited preferential preservation despite similar engagement in HR-FC. Together, these findings indicate that network-level ALFF captures a distinct yet complementary layer of functional dynamics, with a temporal profile distinct from functional connectivity. Spontaneous BOLD dynamics during acute hypoxia reflect structured network-level modulation rather than a uniform suppression attributable solely to reduced oxygen availability. These findings support a conceptual framework of cerebral oxygen budgeting , in which metabolic constraints reshape functional dynamics across brain networks.

Abstract Background Flow‐related ghost artifact from a 3D Magnetization Prepared Rapid Gradient Echo (MPRAGE) sequence results from unsaturated magnetization of incoming arterial flow. This is especially common on MR scanners equipped with smaller radiofrequency (RF) transmit coils. A high‐performance compact 3T (C3T) scanner features a smaller RF‐transmit coil (inner diameter 37 cm, length 40 cm), leading to a rapid fall‐off of the B1 field below the neck. This configuration results in more intense flow‐related ghost artifacts, especially in younger patients. Purpose The C3T scanner's smaller RF‐transmit coil provides RF field coverage over the brain region, causing bright in‐flow arterial signals and flow‐related artifacts in the conventional 3D‐MPRAGE scans. The purpose of this study is to suppress these artifacts by adding a RF saturation band (RFSB) pulses to the 3D‐MPRAGE sequence. Methods The RFSB was added to the 3D‐MPRAGE sequence as a preparation pulse option. To test the effectiveness, 37 subjects were scanned on the C3T under an IRB‐approved protocol using 3D‐MPRAGE with and without RFSB. Ten of those subjects underwent repeated scans with and without RFSB to evaluate test‐retest reliability. A consensus evaluation by two neuroradiologists was performed on all data to compare signal to noise ratio, image contrast, presence of artifacts, and diagnostic confidence. Quantitative analysis included calculating test‐retest differences by image subtraction and evaluating the variance in flow‐artifact‐induced image intensity between the scans with and without RFSB. Additionally, one subject was scanned on a whole‐body 3T scanner using a transmit/receive (T/R) head coil to demonstrate the method's applicability across different MRI platforms as a proof of concept. Results The Wilcoxon signed‐rank test of the neuroradiologist evaluations showed a significant reduction in artifacts and an improvement in diagnostic confidence in the posterior fossa region with and without RFSB ( p < 0.0001). Test–retest analysis showed that adding RFSB significantly reduced image intensity variability in the cerebellum, even among subjects without visible flow artifacts. The normalized difference decreased from 8.71% to 6.41% ( p = 0.0059), suggesting improved image reliability in regions prone to flow‐related artifacts. Additionally, similar findings were observed in scans on a whole‐body 3T with a T/R head coil, demonstrating the broader applicability of this method. Conclusion Incorporating RFSB into 3D‐MPRAGE scans effectively reduces flow‐related ghost artifact on the C3T scanner, improving image quality and diagnostic confidence. These findings suggest that the proposed method could be widely implemented across MRI systems utilizing a smaller RF‐transmit coil.

In blood-oxygen-level-dependent (BOLD)-based resting-state functional (RS-fMRI) studies, usage of multi-echo echo-planar-imaging (ME-EPI) is limited due to unacceptable late echo times when high spatial resolution is used. Equipped with high-performance gradients, the compact 3T MRI system (C3T) enables a three-echo whole-brain ME-EPI protocol with smaller than 2.5 mm isotropic voxel and shorter than 1 s repetition time, as required in landmark fMRI studies. The performance of the ME-EPI was comprehensively evaluated with signal variance reduction and region-of-interest-, seed- and independent-component-analysis-based functional connectivity analyses and compared with a counterpart of single-echo EPI with the shortest TR possible. Through the multi-echo combination, the thermal noise level is reduced. Functional connectivity, as well as signal intensity, are recovered in the medial orbital sulcus and anterior transverse collateral sulcus in ME-EPI. It is demonstrated that ME-EPI provides superior sensitivity and accuracy for detecting functional connectivity and/or brain networks in comparison with single-echo EPI. In conclusion, the high-performance gradient enabled high-spatial-temporal resolution ME-EPI would be the method of choice for RS-fMRI study on the C3T.

Objective This study investigates a locally low-rank (LLR) denoising algorithm applied to source images from a clinical task-based functional MRI (fMRI) exam before post-processing for improving statistical confidence of task-based activation maps. Methods Task-based motor and language fMRI was obtained in eleven healthy volunteers under an IRB approved protocol. LLR denoising was then applied to raw complex-valued image data before fMRI processing. Activation maps generated from conventional non-denoised (control) data were compared with maps derived from LLR-denoised image data. Four board-certified neuroradiologists completed consensus assessment of activation maps; region-specific and aggregate motor and language consensus thresholds were then compared with nonparametric statistical tests. Additional evaluation included retrospective truncation of exam data without and with LLR denoising; a ROI-based analysis tracked t-statistics and temporal SNR (tSNR) as scan durations decreased. A test-retest assessment was performed; retest data were matched with initial test data and compared for one subject. Results fMRI activation maps generated from LLR-denoised data predominantly exhibited statistically significant ( p = 4.88×10 –4 to p = 0.042; one p = 0.062) increases in consensus t-statistic thresholds for motor and language activation maps. Following data truncation, LLR data showed task-specific increases in t-statistics and tSNR respectively exceeding 20 and 50% compared to control. LLR denoising enabled truncation of exam durations while preserving cluster volumes at fixed thresholds. Test-retest showed variable activation with LLR data thresholded higher in matching initial test data. Conclusion LLR denoising affords robust increases in t-statistics on fMRI activation maps compared to routine processing, and offers potential for reduced scan duration while preserving map quality.

BackgroundA low‐cryogen, compact 3T (C3T) MRI scanner with high‐performance gradients capable of simultaneously achieving 80 mT/m gradient amplitude and 700 T/m/second slew rate has been in use to study research patients since March 2016 but has not been implemented in the clinical practice.PurposeTo compare head MRI examinations obtained with the C3T system and a conventional whole‐body 3T (WB3T) scanner in seven parameters across five commonly used brain imaging sequences.Study TypeProspective.SubjectsThirty patients with a clinically indicated head MRI.Sequence 3T; T1 FLAIR, T1 MP‐RAGE, 3D T2 FLAIR, T2 FSE, and DWI.AssessmentAll patients tolerated the scans well. Three board‐certified neuroradiologists scored the comparative quality of C3T and WB3T images in blinded fashion using a five‐point Likert scale in terms of: signal‐to‐noise ratio, lesion conspicuity, motion artifact, gray/white matter contrast, cerebellar folia, susceptibility artifact, and overall quality.Statistical TestLeft‐sided, right‐sided, and two‐sided Wilcoxon signed rank test; Fisher's method. A P value <0.05 was considered statistically significant.ResultsThe C3T system performed better than the WB3T in virtually all comparisons, except for motion artifacts for the T1 FLAIR and T1 MP‐RAGE sequences, where the WB3T system was deemed better. When combining all sequences together, the C3T system outperformed the WB3T system in all image quality parameters evaluated, except for motion artifact (P = 0.13).Data ConclusionThe C3T scanner provided better overall image quality for all sequences, and performed better in all individual categories, except for motion artifact on the T1 FLAIR and T1 MP‐RAGE.Level of Evidence2Technical Efficacy Stage1

PurposeTo demonstrate the feasibility of pseudo‐continuous arterial‐spin–labeled (pCASL) imaging with 3D fast‐spin‐echo stack‐of‐spirals on a compact 3T scanner (C3T), to perform trajectory correction for eddy‐current–induced deviations in the spiral readout of pCASL imaging, and to assess the correction effect on perfusion‐related images with high‐performance gradients (80 mT/m, 700T/m/s) of the C3T.MethodsTo track eddy‐current–induced artifacts with Archimedean spiral readout, the spiral readout in pCASL imaging was performed with 5 different peak gradient slew rate (Smax) values ranging from 70 to 500 T/m/s. The trajectory for each Smax was measured using a dynamic field camera and applied in a density‐compensated gridding image reconstruction in addition to the nominal trajectory. The effect of the trajectory correction was assessed with perfusion‐weighted (ΔM) images and proton‐density–weighted images as well as cerebral blood flow (CBF) maps, obtained from 10 healthy volunteers.ResultsBlurring artifact on ΔM images was mitigated by the trajectory correction. CBF values on the left and right calcarine cortices showed no significant difference after correction. Also, the signal‐to‐noise ratio of ΔM images improved, on average, by 7.6% after correction (P < .001). The greatest improvement of 12.1% on ΔM images was achieved with a spiral readout using Smax of 300~400 T/m/s.ConclusionEddy currents can cause spiral trajectory deviation, which leads to deformation of the CBF map even in cases of low value Smax. The trajectory correction for spiral‐readout–based pCASL produces more reliable results for perfusion imaging. These results suggest that pCASL is feasible on C3T with high‐performance gradients.

BackgroundDistortion‐free, high‐resolution diffusion imaging using DIADEM (Distortion‐free Imaging: A Double Encoding Method), proposed recently, has great potential for clinical applications. However, it can suffer from prolonged scan times and its reliability for quantitative diffusion imaging has not been evaluated.PurposeTo investigate the clinical feasibility of DIADEM‐based high‐resolution diffusion imaging on a novel compact 3T (C3T) by evaluating the reliability of quantitative diffusion measurements and utilizing both the high‐performance gradients (80 mT/m, 700 T/m/s) and the sequence optimization with the navigator acquisition window reduction and simultaneous multislice (multiband) imaging.Study TypeProspective feasibility study.Phantom/SubjectsDiffusion quality control phantom scans to evaluate the reliability of quantitative diffusion measurements; 36 normal control scans for B0‐field mapping; six healthy and two patient subject scans with a brain tumor for comparisons of diffusion and anatomical imaging.Field Strength/Sequence3T; the standard single‐shot echo‐planar‐imaging (EPI), multishot DIADEM diffusion, and anatomical (2D‐FSE [fast‐spin‐echo], 2D‐FLAIR [fluid‐attenuated‐inversion‐recovery], and 3D‐MPRAGE [magnetization prepared rapid acquisition gradient echo]) imaging.AssessmentThe scan time reduction, the reliability of quantitative diffusion measurements, and the clinical efficacy for high‐resolution diffusion imaging in healthy control and brain tumor volunteers.Statistical TestBland–Altman analysis.ResultsThe scan time for high in‐plane (0.86 mm2) resolution, distortion‐free, and whole brain diffusion imaging were reduced from 10 to 5 minutes with the sequence optimizations. All of the mean apparent diffusion coefficient (ADC) values in phantom were within the 95% confidence interval in the Bland–Altman plot. The proposed acquisition with a total off‐resonance coverage of 597.2 Hz wider than the expected bandwidth of 500 Hz in human brain could yield a distortion‐free image without foldover artifacts. Compared with EPI, therefore, this approach allowed direct image matching with the anatomical images and enabled improved delineation of the tumor boundaries.Data ConclusionThe proposed high‐resolution diffusion imaging approach is clinically feasible on C3T due to a combination of hardware and sequence improvements.Level of Evidence3Technical EfficacyStage 1 J. Magn. Reson. Imaging 2020;51:296–310.

PurposeTo build and evaluate a small‐footprint, lightweight, high‐performance 3T MRI scanner for advanced brain imaging with image quality that is equal to or better than conventional whole‐body clinical 3T MRI scanners, while achieving substantial reductions in installation costs.MethodsA conduction‐cooled magnet was developed that uses less than 12 liters of liquid helium in a gas‐charged sealed system, and standard NbTi wire, and weighs approximately 2000 kg. A 42‐cm inner‐diameter gradient coil with asymmetric transverse axes was developed to provide patient access for head and extremity exams, while minimizing magnet‐gradient interactions that adversely affect image quality. The gradient coil was designed to achieve simultaneous operation of 80‐mT/m peak gradient amplitude at a slew rate of 700 T/m/s on each gradient axis using readily available 1‐MVA gradient drivers.ResultsIn a comparison of anatomical imaging in 16 patients using T2‐weighted 3D fluid‐attenuated inversion recovery (FLAIR) between the compact 3T and whole‐body 3T, image quality was assessed as equivalent to or better across several metrics. The ability to fully use a high slew rate of 700 T/m/s simultaneously with 80‐mT/m maximum gradient amplitude resulted in improvements in image quality across EPI, DWI, and anatomical imaging of the brain.ConclusionsThe compact 3T MRI system has been in continuous operation at the Mayo Clinic since March 2016. To date, over 200 patient studies have been completed, including 96 comparison studies with a clinical 3T whole‐body MRI. The increased gradient performance has reliably resulted in consistently improved image quality.