T1 mapping from routine 3D T1-weighted inversion recovery sequences in clinical practice: comparison against reference inversion recovery fast field echo T1 scans and feasibility in multiple sclerosis.

BACKGROUND AND PURPOSE: Quantitative T1 mapping can be an essential tool for assessing tissue injury in multiple sclerosis (MS). We introduce T1-REQUIRE, a method that converts a single high-resolution anatomical 3D T1-weighted Turbo Field Echo (3DT1TFE) scan into a parametric T1 map that could be used for quantitative assessment of tissue damage. We present the accuracy and feasibility of this method in MS. METHODS: 14 subjects with relapsing-remitting MS and 10 healthy subjects were examined. T1 maps were generated from 3DT1TFE images using T1-REQUIRE, which estimates T1 values using MR signal equations and internal tissue reference T1 values. Estimated T1 of lesions, white, and gray matter regions were compared with reference Inversion-Recovery Fast Field Echo T1 values and analyzed via correlation and Bland-Altman (BA) statistics. RESULTS: 159 T1-weighted (T1W) hypointense MS lesions and 288 gray matter regions were examined. T1 values for MS lesions showed a Pearson's correlation of r = 0.81 (p < 0.000), R2 = 0.65, and Bias = 4.18%. BA statistics showed a mean difference of -53.95 ms and limits of agreement (LOA) of -344.20 and 236.30 ms. Non-lesional normal-appearing white matter had a correlation coefficient of r = 0.82 (p < 0.000), R2 = 0.67, Bias = 8.78%, mean difference of 73.87 ms, and LOA of -55.67 and 203.41 ms. CONCLUSIONS: We demonstrate the feasibility of retroactively derived high-resolution T1 maps from routinely acquired anatomical images, which could be used to quantify tissue pathology in MS. The results of this study will set the stage for testing this method in larger clinical studies for examining MS disease activity and progression.

Flow augmentation therapies preserve brain network integrity and hemodynamics in a canine permanent occlusion model.

The acute phase of ischemic stroke presents a critical window for therapeutic intervention, where novel approaches such as hyper-acute cerebral flow augmentation offer promising avenues for neuroprotection. In this study, we investigated the effects of two such therapies, NEH (a combination of norepinephrine and hydralazine) and Sanguinate (pegylated bovine carboxyhemoglobin), on resting-state functional connectivity, global mean signal (GMS), and blood oxygen level-dependent (BOLD) time lag in a pre-clinical canine model of stroke via permanent occlusion of the middle cerebral artery (total of n = 40 IACUC-approved mongrel canines randomly split into control/natural history and two treatment groups). Utilizing group independent component analysis (ICA), we identified and examined the integrity of sensorimotor and visual networks both pre- and post-occlusion, across treatment and control groups. Our results demonstrated that while the control group exhibited significant disruptions in these networks following stroke, the treatment groups showed remarkable preservation of network integrity. Voxel-wise functional connectivity analysis revealed less pronounced alterations in the treatment groups, suggesting maintained neural connections. Notably, the treatments stabilized GMS, with only minimal reductions observed post-occlusion compared to significant decreases in the control group. Furthermore, BOLD time-lag unity plots indicated that NEH and Sanguinate maintained consistent hemodynamic response timing, as evidenced by tighter clustering around the line of unity, suggesting a potential neuroprotective effect. These findings were underscored by robust statistical analyses, including paired T-tests and Mann-Whitney U tests, which confirmed the significance of the connectivity changes observed. The correlation of BOLD time-lag variations with neuroimaging functional biomarkers highlighted the impact of stroke and the efficacy of early therapeutic interventions. Our study supports the further study of flow augmentation therapies such as NEH and Sanguinate in stroke treatment protocols and suggests flow augmentation therapies should be further explored in an effort to improve patient outcomes.

Increased force and elastic energy storage are not the mechanisms that improve jump performance with accentuated eccentric loading during a constrained vertical jump.

Accentuated eccentric loading (AEL) involves higher load applied during the eccentric phase of a stretch-shortening cycle movement, followed by a sudden removal of load before the concentric phase. Previous studies suggest that AEL enhances human countermovement jump performance, however the mechanism is not fully understood. Here we explore whether isolating additional load during the countermovement is sufficient to increase ground reaction force, and hence elastic energy stored, at the start of the upward movement and whether this leads to increased jump height or power generation. We conducted a trunk-constrained vertical jump test on a custom-built device to isolate the effect of additional load while controlling for effects of squat depth, arm swing, and coordination. Twelve healthy, recreationally active adults (7 males, 5 females) performed maximal jumps without AEL, followed by randomised AEL conditions prescribed as a percentage of body mass (10%, 20%, and 30%), before repeating jumps without AEL. No significant changes in vertical ground reaction force at the turning point were observed. High load AEL conditions (20% and 30% body weight) led to slight reductions in jump height, primarily due to decreased hip joint and centre of mass work. AEL conditions did not alter peak or integrated activation levels of the knee extensor muscles. The constrained movement task used here, which excluded potential contributions of trunk motion, arm swing, rate of descent, squat depth, and point of load application, allows the conclusion that increased elastic energy return is not the primary mechanism for potentiating effects of AEL on jump performance.

Efficacy Assessment of Cerebral Perfusion Augmentation through Functional Connectivity in an Acute Canine Stroke Model.

BACKGROUND AND PURPOSE: Ischemic stroke disrupts functional connectivity within the brain's resting-state networks (RSNs), impacting recovery. This study evaluates the effects of norepinephrine and hydralazine (NEH), a cerebral perfusion augmentation therapy, on RSN integrity in a hyperacute canine stroke model. MATERIALS AND METHODS: Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Postocclusion, the treatment group received intra-arterial norepinephrine (0.1-1.52 µg/kg/min, adjusted for 25-45 mm Hg above baseline mean arterial pressure) and hydralazine (20 mg). Resting-state fMRI (rs-fMRI) data were acquired with a 3T scanner by using a blood oxygen level dependent-EPI sequence (TR/TE = 1400 ms/20 ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm full width at half maximum), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis and weighted whole-brain ROI-to-ROI connectome, pre- and post-MCAO. RESULTS: NEH therapy significantly maintained connectivity post-MCAO in the higher-order visual and parietal RSNs, as evidenced by thresholded statistical mapping (threshold-free cluster enhancement P corr > .95). However, this preservation was network-dependent, with no significant (P corr < .95) changes in the primary visual and sensorimotor networks. CONCLUSIONS: NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity after ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable end point for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation.

Dopamine Increases Accuracy and Lengthens Deliberation Time in Explicit Motor Skill Learning.

Although animal research implicates a central role for dopamine in motor skill learning, a direct causal link has yet to be established in neurotypical humans. Here, we tested if a pharmacological manipulation of dopamine alters motor learning, using a paradigm which engaged explicit, goal-directed strategies. Participants (27 females; 11 males; aged 18-29 years) first consumed either 100 mg of levodopa (n = 19), a dopamine precursor that increases dopamine availability, or placebo (n = 19). Then, during training, participants learnt the explicit strategy of aiming away from presented targets by instructed angles of varying sizes. Targets jumped mid-movement by the instructed aiming angle. Task success was thus contingent upon aiming accuracy and not speed. The effect of the dopamine manipulations on skill learning was assessed during training and after an overnight follow-up. Increasing dopamine availability at training improved aiming accuracy and lengthened reaction times, particularly for larger, more difficult aiming angles, both at training and, importantly, at follow-up, despite prominent session-by-session performance improvements in both accuracy and speed. Exogenous dopamine thus seems to result in a learnt, persistent propensity to better adhere to task goals. Results support the proposal that dopamine is important in engagement of instrumental motivation to optimize adherence to task goals, particularly when learning to execute goal-directed strategies in motor skill learning.

Quantification of Collateral Supply with Local-AIF Dynamic Susceptibility Contrast MRI Predicts Infarct Growth.

BACKGROUND AND PURPOSE: In ischemic stroke, leptomeningeal collaterals can provide delayed and dispersed compensatory blood flow to tissue-at-risk despite an occlusion and can impact treatment response and infarct growth. The purpose of this work is to test the hypothesis that inclusion of this delayed and dispersed flow with an appropriately calculated Local Arterial Input Function (Local-AIF) is needed to quantify the degree of collateral blood supply in tissue distal to an occlusion. MATERIALS AND METHODS: Seven experiments were conducted in a pre-clinical middle cerebral artery occlusion model. Dynamic susceptibility contrast MRI was imaged and post-processed to yield quantitative cerebral blood flow (qCBF) maps with both a traditionally chosen single arterial input function applied globally to the whole brain (i.e. "Global-AIF") and a delay and dispersion corrected AIF (i.e. "Local-AIF") that is sensitive to retrograde flow. Leptomeningeal collateral arterial recruitment was quantified with a pial collateral score from x-ray angiograms, and infarct growth calculated from serially acquired diffusion weighted MRI scans. RESULTS: The degree of collateralization at x-ray correlated more strongly with qCBF using the Local-AIF in the ischemic penumbra (R2=0.81) than traditionally chosen Global-AIF (R2=0.05). qCBF using a Local-AIF was negatively correlated (less infarct progression as perfusion increased) with infarct growth (R2 = 0.79) more strongly than a Global-AIF (R2=0.02). CONCLUSIONS: In acute stroke, qCBF calculated with a Local-AIF is more accurate for assessing tissue status and collateral supply than traditionally chosen Global-AIFs. These findings support use of a Local-AIF that corrects for delayed and dispersed retrograde flow in determining quantitative tissue perfusion with collateral supply in occlusive disease. ABBREVIATIONS: MRI = magnetic resonance imaging; DSC = dynamic susceptibility contrast; PCS = pial collateral score; MCAO = middle cerebral artery occlusion; MCA = middle cerebral artery; AIF = arterial input function; rCBF = relative cerebral blood flow; qCBF = quantitative cerebral blood flow.

Quantification of Collateral Supply with Local-AIF Dynamic Susceptibility Contrast MRI Predicts Infarct Growth.

Background and purpose: In ischemic stroke, leptomeningeal collaterals can provide compensatory blood flow to tissue at risk despite an occlusion, and impact treatment response and infarct growth. The purpose of this work is to test the hypothesis that local perfusion with an appropriate Local Arterial Input Function (AIF) is needed to quantify the degree of collateral blood supply in tissue distal to an occlusion. Materials and methods: Seven experiments were conducted in a pre-clinical middle cerebral artery occlusion model. Magnetic resonance dynamic susceptibility contrast (DSC) was imaged and post-processed as cerebral blood flow maps with both a traditionally chosen single arterial input function (AIF) applied globally to the whole brain (i.e. "Global-AIF") and a novel automatic delay and dispersion corrected AIF (i.e. "Local AIF") that is sensitive to retrograde flow. Pial collateral recruitment was assessed from x-ray angiograms and infarct growth via serially acquired diffusion weighted MRI scans both blinded to DSC. Results: The degree of collateralization at x-ray correlated strongly with quantitative perfusion determined using the Local AIF in the ischemic penumbra (R2=0.81) compared to a traditionally chosen Global-AIF (R2=0.05). Quantitative perfusion calculated using a Local-AIF was negatively correlated (less infarct progression as local perfusion increased) with infarct growth (R2 = 0.79) compared to Global-AIF (R2=0.02). Conclusions: Local DSC perfusion with a Local-AIF is more accurate for assessing tissue status and degree of leptomeningeal collateralization than traditionally chosen AIFs. These findings support use of a Local-AIF in determining quantitative tissue perfusion with collateral supply in occlusive disease.

Temporal Changes on Postgadolinium MR Vessel Wall Imaging Captures Enhancement Kinetics of Intracranial Atherosclerotic Plaques and Aneurysms.

BACKGROUND AND PURPOSE: Analysis of vessel wall contrast kinetics (ie, wash-in/washout) is a promising method for the diagnosis and risk-stratification of intracranial atherosclerotic disease plaque (ICAD-P) and the intracranial aneurysm walls (IA-W). We used black-blood MR imaging or MR vessel wall imaging to evaluate the temporal relationship of gadolinium contrast uptake kinetics in ICAD-Ps and IA-Ws compared with normal anatomic reference structures. MATERIALS AND METHODS: Patients with ICAD-Ps or IAs who underwent MR vessel wall imaging with precontrast, early postcontrast (5-15 minutes), and delayed postcontrast (20-30 minutes) 3D T1-weighted TSE sequences were retrospectively studied. ROIs of a standardized diameter (2 mm) were used to measure the signal intensities of the cavernous sinus, pituitary infundibulum, temporalis muscle, and choroid plexus. Point ROIs were used for ICAD-Ps and IA-Ws. All ROI signal intensities were normalized to white matter signal intensity obtained using ROIs of 10-mm diameter. Measurements were acquired on precontrast, early postcontrast, and delayed postcontrast 3D T1 TSE sequences for each patient. RESULTS: Ten patients with 17 symptomatic ICAD-Ps and 30 patients with 34 IA-Ws were included and demonstrated persisting contrast uptake (P < .001) of 7.21% and 10.54% beyond the early phase (5-15 minutes postcontrast) and in the delayed phase (20-30 minutes postcontrast) on postcontrast MR vessel wall imaging. However, normal anatomic reference structures including the pituitary infundibulum and cavernous sinus demonstrated a paradoxical contrast washout in the delayed phase. In both ICAD-Ps and IA-Ws, the greatest percentage of quantitative enhancement (>70%-90%) occurred in the early phase of postcontrast imaging, consistent with the rapid contrast uptake kinetics of neurovascular pathology. CONCLUSIONS: Using standard MR vessel wall imaging techniques, our results demonstrate the effects of gadolinium contrast uptake kinetics in ICAD-Ps and IA-Ws with extended accumulating enhancement into the delayed phase (> 15 minutes) as opposed to normal anatomic reference structures that conversely exhibit decreasing enhancement. Because these relative differences are used to assess qualitative patterns of ICAD-P and IA-W enhancement, our findings highlight the importance of standardizing acquisition time points and MR vessel wall imaging protocols to interpret pathologic enhancement for the risk stratification of cerebrovascular pathologies.