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Background and Purpose: CT imaging exposes patients to ionizing radiation. MR imaging is radiation free but previously has not been able to produce diagnostic-quality images of bone on a timeline suitable for clinical use. We developed automated motion correction and use deep learning to generate pseudo-CT images from MR images. We aim to evaluate whether motion-corrected pseudo-CT produces cranial images that have potential to be acceptable for clinical use., Materials and Methods: Patients younger than age 18 who underwent CT imaging of the head for either trauma or evaluation of cranial suture patency were recruited. Subjects underwent a 5-minute golden-angle stack-of-stars radial volumetric interpolated breath-hold MR image. Motion correction was applied to the MR imaging followed by a deep learning-based method to generate pseudo-CT images. CT and pseudo-CT images were evaluated and, based on indication for imaging, either presence of skull fracture or cranial suture patency was first recorded while viewing the MR imaging-based pseudo-CT and then recorded while viewing the clinical CT., Results: A total of 12 patients underwent CT and MR imaging to evaluate suture patency, and 60 patients underwent CT and MR imaging for evaluation of head trauma. For cranial suture patency, pseudo-CT had 100% specificity and 100% sensitivity for the identification of suture closure. For identification of skull fractures, pseudo-CT had 100% specificity and 90% sensitivity., Conclusions: Our early results show that automated motion-corrected and deep learning-generated pseudo-CT images of the pediatric skull have potential for clinical use and offer a high level of diagnostic accuracy when compared with standard CT scans., (© 2024 by American Journal of Neuroradiology.)

Purpose: To introduce a novel deep model-based architecture (DMBA), SPICER, that uses pairs of noisy and undersampled k-space measurements of the same object to jointly train a model for MRI reconstruction and automatic coil sensitivity estimation., Methods: SPICER consists of two modules to simultaneously reconstructs accurate MR images and estimates high-quality coil sensitivity maps (CSMs). The first module, CSM estimation module, uses a convolutional neural network (CNN) to estimate CSMs from the raw measurements. The second module, DMBA-based MRI reconstruction module, forms reconstructed images from the input measurements and the estimated CSMs using both the physical measurement model and learned CNN prior. With the benefit of our self-supervised learning strategy, SPICER can be efficiently trained without any fully sampled reference data., Results: We validate SPICER on both open-access datasets and experimentally collected data, showing that it can achieve state-of-the-art performance in highly accelerated data acquisition settings (up to 10 × $$ 10\times $$ ). Our results also highlight the importance of different modules of SPICER-including the DMBA, the CSM estimation, and the SPICER training loss-on the final performance of the method. Moreover, SPICER can estimate better CSMs than pre-estimation methods especially when the ACS data is limited., Conclusion: Despite being trained on noisy undersampled data, SPICER can reconstruct high-quality images and CSMs in highly undersampled settings, which outperforms other self-supervised learning methods and matches the performance of the well-known E2E-VarNet trained on fully sampled ground-truth data., (© 2024 International Society for Magnetic Resonance in Medicine.)

Abnormal oxygen extraction fraction (OEF), a putative biomarker of cerebral metabolic stress, may indicate compromised oxygen delivery and ischemic vulnerability in patients with sickle cell disease (SCD). Elevated OEF was observed at the tissue level across the brain using an asymmetric spin echo (ASE) MR method, while variable global OEFs were found from the superior sagittal sinus (SSS) using a T2-relaxation-under-spin-tagging (TRUST) MRI method with different calibration models. In this study, we aimed to compare the average ASE-OEF in the SSS drainage territory and TRUST-OEF in the SSS from the same SCD patients and healthy controls. 74 participants (SCD: N = 49; controls: N = 25) underwent brain MRI. TRUST-OEF was quantified using the Lu-bovine, Bush-HbA and Li-Bush-HbS models. ASE-OEF and TRUST-OEF were significantly associated in healthy controls after controlling for hematocrit using the Lu-bovine or the Bush-HbA model. However, no association was found between ASE-OEF and TRUST-OEF in patients with SCD using either the Bush-HbA or the Li-Bush-HbS model. Plausible explanations include a discordance between spatially volume-averaged oxygenation brain tissue and flow-weighted volume-averaged oxygenation in SSS or sub-optimal calibration in SCD. Further work is needed to refine and validate non-invasive MR OEF measurements in SCD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The kidneys maintain fluid-electrolyte balance and excrete waste in the presence of constant fluctuations in plasma volume and systemic blood pressure. The kidneys perform these functions to control capillary perfusion and glomerular filtration by modulating the mechanisms of autoregulation. An effect of these modulations are spontaneous, natural fluctuations in glomerular perfusion. Numerous other mechanisms can lead to fluctuations in perfusion and flow. The ability to monitor these spontaneous physiological fluctuations in vivo could facilitate the early detection of kidney disease. The goal of this work was to investigate the use of resting-state magnetic resonance imaging (rsMRI) to detect spontaneous physiological fluctuations in the kidney. We performed rsMRI of rat kidneys in vivo over 10 min, applying motion correction to resolve time series in each voxel. We observed spatially variable, spontaneous fluctuations in rsMRI signal between 0 and 0.3 Hz, in frequency bands associated with autoregulatory mechanisms. We further applied rsMRI to investigate changes in these fluctuations in a rat model of diabetic nephropathy. Spectral analysis was performed on time series of rsMRI signals in the kidney cortex and medulla. The power from spectra in specific frequency bands from the cortex correlated with severity of glomerular pathology caused by diabetic nephropathy. Finally, we investigated the feasibility of using rsMRI of the human kidney in two participants, observing the presence of similar, spatially variable fluctuations. This approach may enable a range of preclinical and clinical investigations of kidney function and facilitate the development of new therapies to improve outcomes in patients with kidney disease. NEW & NOTEWORTHY This work demonstrates the development and use of resting-state MRI to detect low-frequency, spontaneous physiological fluctuations in the kidney consistent with previously observed fluctuations in perfusion and potentially due to autoregulatory function. These fluctuations are detectable in rat and human kidneys, and the power of these fluctuations is affected by diabetic nephropathy in rats.

Background: MRI has a rapidly growing role in radiation therapy (RT) for treatment planning, real-time image guidance, and beam gating (e.g., MRI-Linac). Free-breathing 4D-MRI is desirable in respiratory motion management for therapy. Moreover, high-quality 3D-MRIs without motion artifacts are needed to delineate lesions. Existing MRI methods require multiple scans with lengthy acquisition times or are limited by low spatial resolution, contrast, and signal-to-noise ratio., Purpose: We developed a novel method to obtain motion-resolved 4D-MRIs and motion-integrated 3D-MRI reconstruction using a single rapid (35-45 s scan on a 0.35 T MRI-Linac., Methods: Golden-angle radial stack-of-stars MRI scans were acquired from a respiratory motion phantom and 12 healthy volunteers (n = 12) on a 0.35 T MRI-Linac. A self-navigated method was employed to detect respiratory motion using 2000 (acquisition time = 5-7 min) and the first 200 spokes (acquisition time = 35-45 s). Multi-coil non-uniform fast Fourier transform (MCNUFFT), compressed sensing (CS), and deep-learning Phase2Phase (P2P) methods were employed to reconstruct motion-resolved 4D-MRI using 2000 spokes (MCNUFFT2000) and 200 spokes (CS200 and P2P200). Deformable motion vector fields (MVFs) were computed from the 4D-MRIs and used to reconstruct motion-corrected 3D-MRIs with the MOtion Transformation Integrated forward-Fourier (MOTIF) method. Image quality was evaluated quantitatively using the structural similarity index measure (SSIM) and the root mean square error (RMSE), and qualitatively in a blinded radiological review., Results: Evaluation using the respiratory motion phantom experiment showed that the proposed method reversed the effects of motion blurring and restored edge sharpness. In the human study, P2P200 had smaller inaccuracy in MVFs estimation than CS200. P2P200 had significantly greater SSIMs (p < 0.0001) and smaller RMSEs (p < 0.001) than CS200 in motion-resolved 4D-MRI and motion-corrected 3D-MRI. The radiological review found that MOTIF 3D-MRIs using MCNUFFT2000 exhibited the highest image quality (scoring > 8 out of 10), followed by P2P200 (scoring > 5 out of 10), and then motion-uncorrected (scoring < 3 out of 10) in sharpness, contrast, and artifact-freeness., Conclusions: We have successfully demonstrated a method for respiratory motion management for MRI-guided RT. The method integrated self-navigated respiratory motion detection, deep-learning P2P 4D-MRI reconstruction, and a motion integrated reconstruction (MOTIF) for 3D-MRI using a single rapid MRI scan (35-45 s) on a 0.35 T MRI-Linac system., (© 2023 American Association of Physicists in Medicine.)

Children with sickle cell disease (SCD) demonstrate cerebral hemodynamic stress and are at high risk of strokes. We hypothesized that curative hematopoietic stem cell transplant (HSCT) normalizes cerebral hemodynamics in children with SCD compared with pre-transplant baseline. Whole-brain cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were measured by magnetic resonance imaging 1 to 3 months before and 12 to 24 months after HSCT in 10 children with SCD. Three children had prior overt strokes, 5 children had prior silent strokes, and 1 child had abnormal transcranial Doppler ultrasound velocities. CBF and OEF of HSCT recipients were compared with non-SCD control participants and with SCD participants receiving chronic red blood cell transfusion therapy (CRTT) before and after a scheduled transfusion. Seven participants received matched sibling donor HSCT, and 3 participants received 8 out of 8 matched unrelated donor HSCT. All received reduced-intensity preparation and maintained engraftment, free of hemolytic anemia and SCD symptoms. Pre-transplant, CBF (93.5 mL/100 g/min) and OEF (36.8%) were elevated compared with non-SCD control participants, declining significantly 1 to 2 years after HSCT (CBF, 72.7 mL/100 g per minute; P = .004; OEF, 27.0%; P = .002), with post-HSCT CBF and OEF similar to non-SCD control participants. Furthermore, HSCT recipients demonstrated greater reduction in CBF (-19.4 mL/100 g/min) and OEF (-8.1%) after HSCT than children with SCD receiving CRTT after a scheduled transfusion (CBF, -0.9 mL/100 g/min; P = .024; OEF, -3.3%; P = .001). Curative HSCT normalizes whole-brain hemodynamics in children with SCD. This restoration of cerebral oxygen reserve may explain stroke protection after HSCT in this high-risk patient population., (© 2023 by The American Society of Hematology.)

Purpose: CT is routinely used to detect cranial abnormalities in pediatric patients with head trauma or craniosynostosis. This study aimed to develop a deep learning method to synthesize pseudo-CT (pCT) images for MR high-resolution pediatric cranial bone imaging to eliminating ionizing radiation from CT., Methods: 3D golden-angle stack-of-stars MRI were obtained from 44 pediatric participants. Two patch-based residual UNets were trained using paired MR and CT patches randomly selected from the whole head (NetWH) or in the vicinity of bone, fractures/sutures, or air (NetBA) to synthesize pCT. A third residual UNet was trained to generate a binary brain mask using only MRI. The pCT images from NetWH (pCT NetWH ) in the brain area and NetBA (pCT NetBA ) in the nonbrain area were combined to generate pCT Com . A manual processing method using inverted MR images was also employed for comparison., Results: pCT Com (68.01 ± 14.83 HU) had significantly smaller mean absolute errors (MAEs) than pCT NetWH (82.58 ± 16.98 HU, P < 0.0001) and pCT NetBA (91.32 ± 17.2 HU, P < 0.0001) in the whole head. Within cranial bone, the MAE of pCT Com (227.92 ± 46.88 HU) was significantly lower than pCT NetWH (287.85 ± 59.46 HU, P < 0.0001) but similar to pCT NetBA (230.20 ± 46.17 HU). Dice similarity coefficient of the segmented bone was significantly higher in pCT Com (0.90 ± 0.02) than in pCT NetWH (0.86 ± 0.04, P < 0.0001), pCT NetBA (0.88 ± 0.03, P < 0.0001), and inverted MR (0.71 ± 0.09, P < 0.0001). Dice similarity coefficient from pCT Com demonstrated significantly reduced age dependence than inverted MRI. Furthermore, pCT Com provided excellent suture and fracture visibility comparable to CT., Conclusion: MR high-resolution pediatric cranial bone imaging may facilitate the clinical translation of a radiation-free MR cranial bone imaging method for pediatric patients., (© 2022 International Society for Magnetic Resonance in Medicine.)

Deep neural networks for medical image reconstruction are traditionally trained using high-quality ground-truth images as training targets. Recent work on Noise2Noise (N2N) has shown the potential of using multiple noisy measurements of the same object as an alternative to having a ground-truth. However, existing N2N-based methods are not suitable for learning from the measurements of an object undergoing nonrigid deformation. This paper addresses this issue by proposing the deformation-compensated learning (DeCoLearn) method for training deep reconstruction networks by compensating for object deformations. A key component of DeCoLearn is a deep registration module, which is jointly trained with the deep reconstruction network without any ground-truth supervision. We validate DeCoLearn on both simulated and experimentally collected magnetic resonance imaging (MRI) data and show that it significantly improves imaging quality.

Purpose: We evaluated the impact of PET respiratory motion correction (MoCo) in a phantom and patients. Moreover, we proposed and examined a PET MoCo approach using motion vector fields (MVFs) from a deep-learning reconstructed short MRI scan., Methods: The evaluation of PET MoCo was performed in a respiratory motion phantom study with varying lesion sizes and tumor to background ratios (TBRs) using a static scan as the ground truth. MRI-based MVFs were derived from either 2000 spokes (MoCo 2000 , 5-6 min acquisition time) using a Fourier transform reconstruction or 200 spokes (MoCo P2P200 , 30-40 s acquisition time) using a deep-learning Phase2Phase (P2P) reconstruction and then incorporated into PET MoCo reconstruction. For six patients with hepatic lesions, the performance of PET MoCo was evaluated using quantitative metrics (SUV max , SUV peak , SUV mean , lesion volume) and a blinded radiological review on lesion conspicuity., Results: MRI-assisted PET MoCo methods provided similar results to static scans across most lesions with varying TBRs in the phantom. Both MoCo 2000 and MoCo P2P200 PET images had significantly higher SUV max , SUV peak , SUV mean and significantly lower lesion volume than non-motion-corrected (non-MoCo) PET images. There was no statistical difference between MoCo 2000 and MoCo P2P200 PET images for SUV max , SUV peak , SUV mean or lesion volume. Both radiological reviewers found that MoCo 2000 and MoCo P2P200 PET significantly improved lesion conspicuity., Conclusion: An MRI-assisted PET MoCo method was evaluated using the ground truth in a phantom study. In patients with hepatic lesions, PET MoCo images improved quantitative and qualitative metrics based on only 30-40 s of MRI motion modeling data., (© 2022 International Society for Magnetic Resonance in Medicine.)

Objective: Head trauma is the most common indication for a CT scan. In this pilot study, the authors assess the feasibility of a 5-minute high-resolution 3D golden-angle (GA) stack-of-stars radial volumetric interpolated breath-hold examination (VIBE) MRI sequence (GA-VIBE) to obtain clinically acceptable cranial bone images and identify cranial vault fractures compared to CT., Methods: Patients younger than 18 years of age presenting after head trauma were eligible for the study. Three clinicians reviewed and assessed 1) slice-by-slice volumetric CT and inverted MR images, and 2) 3D reconstructions obtained from inverted MR images and the gold standard (CT). For each image set, reviewers noted on 5-point Likert scales whether they recommended that a repeat scan be performed and the presence or absence of cranial vault fractures., Results: Thirty-one patients completed MRI after a clinical head CT scan was performed. Based on CT imaging, 8 of 31 patients had cranial fractures. Two of 31 patients were sedated as part of their clinical MRI scan. In 30 (97%) of 31 MRI reviews, clinicians agreed (or strongly agreed) that the image quality was acceptable for clinical diagnosis. Overall, comparing MRI to acceptable gold-standard CT, sensitivity and specificity of fracture detection were 100%. Furthermore, there were no discrepancies between CT and MRI in classification of fracture type or location., Conclusions: When compared with the gold standard (CT), the volumetric and 3D reconstructed images using the GA-VIBE sequence were able to produce clinically acceptable cranial images with excellent ability to detect cranial vault fractures.

Objectives: Respiratory binning of free-breathing magnetic resonance imaging data reduces motion blurring; however, it exacerbates noise and introduces severe artifacts due to undersampling. Deep neural networks can remove artifacts and noise but usually require high-quality ground truth images for training. This study aimed to develop a network that can be trained without this requirement., Materials and Methods: This retrospective study was conducted on 33 participants enrolled between November 2016 and June 2019. Free-breathing magnetic resonance imaging was performed using a radial acquisition. Self-navigation was used to bin the k-space data into 10 respiratory phases. To simulate short acquisitions, subsets of radial spokes were used in reconstructing images with multicoil nonuniform fast Fourier transform (MCNUFFT), compressed sensing (CS), and 2 deep learning methods: UNet3DPhase and Phase2Phase (P2P). UNet3DPhase was trained using a high-quality ground truth, whereas P2P was trained using noisy images with streaking artifacts. Two radiologists blinded to the reconstruction methods independently reviewed the sharpness, contrast, and artifact-freeness of the end-expiration images reconstructed from data collected at 16% of the Nyquist sampling rate. The generalized estimating equation method was used for statistical comparison. Motion vector fields were derived to examine the respiratory motion range of 4-dimensional images reconstructed using different methods., Results: A total of 15 healthy participants and 18 patients with hepatic malignancy (50 ± 15 years, 6 women) were enrolled. Both reviewers found that the UNet3DPhase and P2P images had higher contrast (P < 0.01) and fewer artifacts (P < 0.01) than the CS images. The UNet3DPhase and P2P images were reported to be sharper than the CS images by 1 reviewer (P < 0.01) but not by the other reviewer (P = 0.22, P = 0.18). UNet3DPhase and P2P were similar in sharpness and contrast, whereas UNet3DPhase had fewer artifacts (P < 0.01). The motion vector lengths for the MCNUFFT800 and P2P800 images were comparable (10.5 ± 4.2 mm and 9.9 ± 4.0 mm, respectively), whereas both were significantly larger than CS2000 (7.0 ± 3.9 mm; P < 0.0001) and UNnet3DPhase800 (6.9 ± 3.2; P < 0.0001) images., Conclusions: Without a ground truth, P2P can reconstruct sharp, artifact-free, and high-contrast respiratory motion-resolved images from highly undersampled data. Unlike the CS and UNet3DPhase methods, P2P did not artificially reduce the respiratory motion range., Competing Interests: Conflicts of interest and sources of funding: Siemens Healthineers., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the patient- and tissue-based relationships between cerebral hemodynamic and oxygen metabolic stress, microstructural injury, and infarct location in adults with sickle cell disease (SCD)., Methods: Control participants and patients with SCD underwent brain MRI to quantify cerebral blood flow (CBF), oxygen extraction fraction (OEF), mean diffusivity (MD), and fractional anisotropy (FA) within normal-appearing white matter (NAWM) and infarcts on fluid-attenuated inversion recovery. Multivariable linear regression examined the patient- and voxel-based associations between hemodynamic and metabolic stress (defined as elevated CBF and OEF, respectively), white matter microstructure, and infarct location., Results: Of 83 control participants and patients with SCD, adults with SCD demonstrated increased CBF (50.9 vs 38.8 mL/min/100 g, p < 0.001), increased OEF (0.35 vs 0.25, p < 0.001), increased MD (0.76 vs 0.72 × 10 -3 mm 2 s -1 , p = 0.005), and decreased FA (0.40 vs 0.42, p = 0.021) within NAWM compared to controls. In multivariable analysis, increased OEF (β = 0.19, p = 0.035), but not CBF (β = 0.00, p = 0.340), independently predicted increased MD in the SCD cohort; neither were predictors in controls. On voxel-wise regression, the SCD cohort demonstrated widespread OEF elevation, encompassing deep white matter regions of elevated MD and reduced FA, which spatially extended beyond high-density infarct locations from the SCD cohort., Conclusion: Elevated OEF, a putative index of cerebral oxygen metabolic stress, may provide a metric of ischemic vulnerability that could enable individualization of therapeutic strategies in SCD. The patient- and tissue-based relationships between elevated OEF, elevated MD, and cerebral infarcts suggest that oxygen metabolic stress may underlie microstructural injury prior to the development of cerebral infarcts in SCD., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose: Sickle cell anemia is a blood disorder that alters the morphology and the oxygen affinity of the red blood cells. Cerebral oxygen extraction fraction measurements using quantitative BOLD contrast have been used for assessing inadequate oxygen delivery and the subsequent risk of ischemic stroke in sickle cell anemia. The BOLD signal in MRI studies relies on Δ χ do , the bulk volume susceptibility difference between fully oxygenated and fully deoxygenated blood. Several studies have measured Δ χ do for normal hemoglobin A (HbA). However, it is not known whether the value is different for sickle hemoglobin. In this study, Δ χ do was measured for both HbA and sickle hemoglobin., Methods: Six sickle cell anemia patients and 6 controls were recruited. Various blood oxygenation levels were achieved through in vivo manipulations to keep the blood close to its natural state. To account for the differences in oxygen affinity, Hill's equations were used to translate partial pressure of oxygen to oxygen saturation for HbA, sickle hemoglobin, and fetal hemoglobin (HbF) separately. The pH and PCO 2 corrections were performed. Temperature and magnetic field drift were controlled for. A multivariate generalized linear mixed model with random participant effect was used., Results: Assuming that Δ χ do is similar for HbA and HbF and that Δ χ metHb is 5/4 of Δ χ do for HbA, it was found that the Δ χ do values for HbA and sickle hemoglobin were not statistically significantly different from each other., Conclusion: The same Δ χ do value can be used for both types of hemoglobin in quantitative BOLD analysis., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: To demonstrate a proof of concept for the measurement of myocardial oxygen extraction fraction (mOEF) by a cardiovascular magnetic resonance technique., Methods: The mOEF measurement was performed using an electrocardiogram-triggered double-echo asymmetric spin-echo sequence with EPI readout. Seven healthy volunteers (22-37 years old, 5 females) were recruited and underwent the same imaging scans at rest on 2 different days for reproducibility assessment. Another 5 subjects (23-37 years old, 4 females) underwent cardiovascular magnetic resonance studies at rest and during a handgrip isometric exercise with a 25% of maximal voluntary contraction. Both mOEF and myocardial blood volume values were obtained in septal regions from respective maps., Results: The reproducibility was excellent for the measurements of mOEF in septal myocardium (coefficient of variation: 3.37%) and moderate for myocardial blood volume (coefficient of variation: 19.7%). The average mOEF and myocardial blood volume of 7 subjects at rest were 0.61 ± 0.05 and 11.0 ± 4.3%, respectively. The mOEF agreed well with literature values that were measured by PET in healthy volunteers. In the exercise study, there was no significant change in mOEF (0.61 ± 0.06 vs 0.62 ± 0.07) or myocardial blood volume (12 ± 6% vs 13 ± 4%) from rest to exercise, as expected., Conclusion: The implemented cardiovascular magnetic resonance method shows potential for the quantitative assessment of mOEF in vivo. Future technical work is needed to improve image quality and to further validate mOEF measurements., (© 2021 International Society for Magnetic Resonance in Medicine.)

Objective: Children with sickle cell disease (SCD) experience cognitive deficits even when unaffected by stroke. Using functional connectivity magnetic resonance imaging (MRI) as a potential biomarker of cognitive function, we tested our hypothesis that children with SCD would have decreased functional connectivity, and that children experiencing the greatest metabolic stress, indicated by elevated oxygen extraction fraction, would have the lowest connectivity., Methods: We prospectively obtained brain MRIs and cognitive testing in healthy controls and children with SCD., Results: We analyzed data from 60 participants (20 controls and 40 with sickle cell disease). There was no difference in global cognition or cognitive subdomains between cohorts. However, we found decreased functional connectivity within the sensory-motor, lateral sensory-motor, auditory, salience, and subcortical networks in participants with SCD compared with controls. Further, as white matter oxygen extraction fraction increased, connectivity within the visual (p = 0.008, parameter estimate = -0.760 [95% CI = -1.297, -0.224]), default mode (p = 0.012, parameter estimate = -0.417 [95% CI = -0.731, -0.104]), and cingulo-opercular (p = 0.009, parameter estimate = -0.883 [95% CI = -1.517, -0.250]) networks decreased., Interpretation: We conclude that there is diminished functional connectivity within these anatomically contiguous networks in children with SCD compared with controls, even when differences are not seen with cognitive testing. Increased white matter oxygen extraction fraction was associated with decreased connectivity in select networks. These data suggest that elevated oxygen extraction fraction and disrupted functional connectivity are potentially presymptomatic neuroimaging biomarkers for cognitive decline in SCD. ANN NEUROL 2020;88:995-1008., (© 2020 American Neurological Association.)

Objective: There is an unmet need to perform imaging in young children and obtain CT-equivalent cranial bone images without subjecting the patients to radiation. In this study, the authors propose using a high-resolution fast low-angle shot golden-angle 3D stack-of-stars radial volumetric interpolated breath-hold examination (GA-VIBE) MRI sequence that is intrinsically robust to motion and has enhanced bone versus soft-tissue contrast., Methods: Patients younger than 11 years of age, who underwent clinical head CT scanning for craniosynostosis or other cranial malformations, were eligible for the study. 3D reconstructed images created from the GA-VIBE MRI sequence and the gold-standard CT scan were randomized and presented to 3 blinded reviewers. For all image sets, each reviewer noted the presence or absence of the 6 primary cranial sutures and recorded on 5-point Likert scales whether they recommended a second scan be performed., Results: Eleven patients (median age 1.8 years) underwent MRI after clinical head CT scanning was performed. Five of the 11 patients were sedated. Three clinicians reviewed the images, and there were no cases, either with CT scans or MR images, in which a reviewer agreed a repeat scan was required for diagnosis or surgical planning. The reviewers reported clear imaging of the regions of interest on 99% of the CT reviews and 96% of the MRI reviews. With CT as the standard, the sensitivity and specificity of the GA-VIBE MRI sequence to detect suture closure were 97% and 96%, respectively (n = 198 sutures read)., Conclusions: The 3D reconstructed images using the GA-VIBE sequence in comparison to the CT scans created clinically acceptable cranial images capable of detecting cranial sutures. Future directions include reducing the scan time, improving motion correction, and automating postprocessing for clinical utility.

We have previously characterized the reproducibility of brain tumor relative cerebral blood volume (rCBV) using a dynamic susceptibility contrast magnetic resonance imaging digital reference object across 12 sites using a range of imaging protocols and software platforms. As expected, reproducibility was highest when imaging protocols and software were consistent, but decreased when they were variable. Our goal in this study was to determine the impact of rCBV reproducibility for tumor grade and treatment response classification. We found that varying imaging protocols and software platforms produced a range of optimal thresholds for both tumor grading and treatment response, but the performance of these thresholds was similar. These findings further underscore the importance of standardizing acquisition and analysis protocols across sites and software benchmarking., (© 2020 The Authors. Published by Grapho Publications, LLC.)

Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts ( P = .148). However, whole-brain OEF was significantly different ( P < .001): participants without disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%]), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort ( P = .025 and P = .034 respectively), but higher compared with the CTT cohort ( P = .018 and P = .029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT., (© 2019 by The American Society of Hematology.)

Relative cerebral blood volume (rCBV) cannot be used as a response metric in clinical trials, in part, because of variations in biomarker consistency and associated interpretation across sites, stemming from differences in image acquisition and postprocessing methods (PMs). This study leveraged a dynamic susceptibility contrast magnetic resonance imaging digital reference object to characterize rCBV consistency across 12 sites participating in the Quantitative Imaging Network (QIN), specifically focusing on differences in site-specific imaging protocols (IPs; n = 17), and PMs (n = 19) and differences due to site-specific IPs and PMs (n = 25). Thus, high agreement across sites occurs when 1 managing center processes rCBV despite slight variations in the IP. This result is most likely supported by current initiatives to standardize IPs. However, marked intersite disagreement was observed when site-specific software was applied for rCBV measurements. This study's results have important implications for comparing rCBV values across sites and trials, where variability in PMs could confound the comparison of therapeutic effectiveness and/or any attempts to establish thresholds for categorical response to therapy. To overcome these challenges and ensure the successful use of rCBV as a clinical trial biomarker, we recommend the establishment of qualifying and validating site- and trial-specific criteria for scanners and acquisition methods (eg, using a validated phantom) and the software tools used for dynamic susceptibility contrast magnetic resonance imaging analysis (eg, using a digital reference object where the ground truth is known).

Objectives: In this study, we present a fully automated and robust self-navigated approach to obtain 4-dimensional (4-D) motion-resolved images during free breathing., Materials and Methods: The proposed method, Consistently Acquired Projections for Tuned and Robust Estimation (CAPTURE), is a variant of the stack-of-stars gradient-echo sequence. A 1-D navigator was consistently acquired at a fixed azimuthal angle for all stacks of spokes to reduce nonphysiological signal contamination due to system imperfections. The resulting projections were then "tuned" using complex phase rotation to adapt to scan-to-scan variations, followed by the detection of the respiratory curve. Four-dimensional motion-corrected and uncorrected images were then reconstructed via respiratory and temporal binning, respectively.This Health Insurance Portability and Accountability Act-compliant study was performed with Institutional Review Board approval. A phantom experiment was performed using a custom-made deformable motion phantom with an adjustable frequency and amplitude. For in vivo experiments, 10 healthy participants and 12 liver tumor patients provided informed consent and were imaged with the CAPTURE sequence.Two radiologists, blinded to which images were motion-corrected and which were not, independently reviewed the images and scored the image quality using a 5-point Likert scale., Results: In the respiratory motion phantom experiment, CAPTURE reversed the effects of motion blurring and restored edge sharpness from 36% to 78% of that observed in the images from the static scan.Despite large intra- and intersubject variability in respiration patterns, CAPTURE successfully detected the respiratory motion signal in all participants and significantly improved the image quality according to the subjective radiological assessments of 2 raters (P < 0.05 for both raters) with a 1 to 2-point improvement in the median Likert scores across the whole set of participants. Small lesions (<1 cm in size) which might otherwise be missed on uncorrected images because of motion blurring were more clearly depicted on the CAPTURE images., Conclusions: CAPTURE provides a robust and fully automated solution for obtaining 4-D motion-resolved images in a free-breathing setting. With its unique tuning feature, CAPTURE can adapt to large intersubject and interscan variations. CAPTURE also enables better lesion delineation because of improved image sharpness, thereby increasing the visibility of small lesions.

Objective: To determine mechanisms underlying regional vulnerability to infarction in sickle cell disease (SCD) by measuring voxel-wise cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen utilization (CMRO 2 ) in children with SCD., Methods: Participants underwent brain MRIs to measure voxel-based CBF, OEF, and CMRO 2 . An infarct heat map was created from an independent pediatric SCD cohort with silent infarcts and compared to prospectively obtained OEF maps., Results: Fifty-six participants, 36 children with SCD and 20 controls, completed the study evaluation. Whole-brain CBF (99.2 vs 66.3 mL/100 g/min, p < 0.001), OEF (42.7% vs 28.8%, p < 0.001), and CMRO 2 (3.7 vs 2.5 mL/100 g/min, p < 0.001) were higher in the SCD cohort compared to controls. A region of peak OEF was identified in the deep white matter in the SCD cohort, delineated by a ratio map of average SCD to control OEF voxels. CMRO 2 in this region, which encompassed the CBF nadir, was low relative to all white matter ( p < 0.001). Furthermore, this peak OEF region colocalized with regions of greatest infarct density derived from an independent SCD cohort., Conclusions: Elevated OEF in the deep white matter identifies a signature of metabolically stressed brain tissue at increased stroke risk in pediatric patients with SCD. We propose that border zone physiology, exacerbated by chronic anemic hypoxia, explains the high risk in this region., (© 2018 American Academy of Neurology.)

Blood transfusions are the mainstay of stroke prevention in pediatric sickle cell anemia (SCA), but the physiology conferring this benefit is unclear. Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) are elevated in SCA, likely compensating for reduced arterial oxygen content (CaO 2 ). We hypothesized that exchange transfusions would decrease CBF and OEF by increasing CaO 2 , thereby relieving cerebral oxygen metabolic stress. Twenty-one children with SCA receiving chronic transfusion therapy (CTT) underwent magnetic resonance imaging before and after exchange transfusions. Arterial spin labeling and asymmetric spin echo sequences measured CBF and OEF, respectively, which were compared pre- and posttransfusion. Volumes of tissue with OEF above successive thresholds (36%, 38%, and 40%), as a metric of regional metabolic stress, were compared pre- and posttransfusion. Transfusions increased hemoglobin (Hb; from 9.1 to 10.3 g/dL; P < .001) and decreased Hb S (from 39.7% to 24.3%; P < .001). Transfusions reduced CBF (from 88 to 82.4 mL/100 g per minute; P = .004) and OEF (from 34.4% to 31.2%; P < .001). At all thresholds, transfusions reduced the volume of peak OEF found in the deep white matter, a location at high infarct risk in SCA ( P < .001). Reduction of elevated CBF and OEF, both globally and regionally, suggests that CTT mitigates infarct risk in pediatric SCA by relieving cerebral metabolic stress at patient- and tissue-specific levels., (© 2018 by The American Society of Hematology.)

Background: Large-vessel vasculopathy (LVV) increases stroke risk in pediatric sickle cell disease beyond the baseline elevated stroke risk in this vulnerable population. The mechanisms underlying this added risk and its unique impact on the developing brain are not established., Methods: We analyzed magnetic resonance imaging and angiography scans of 66 children with sickle cell disease and infarcts by infarct density heatmaps and Jacobian determinants, a metric utilized to delineate focal volume change, to investigate if infarct location, volume, frequency, and cerebral atrophy differed among hemispheres with and without LVV., Results: Infarct density heatmaps demonstrated infarct "hot spots" within the deep white matter internal border zone region in both LVV and non-LVV hemispheres, but with greater infarct density and larger infarct volumes in LVV hemispheres (2.2 mL versus 0.25 mL, P < 0.001). Additional scattered cortical infarcts in the internal carotid artery territory occurred in LVV hemispheres, but were rare in non-LVV hemispheres. Jacobian determinants revealed greater atrophy in gray and white matter of the parietal lobes of LVV compared with non-LVV hemispheres., Conclusion: Large-vessel vasculopathy in sickle cell disease appears to increase ischemic vulnerability in the borderzone region, as demonstrated by the increased frequency and extent of infarction within deep white matter, and increased risk of focal atrophy. Scattered infarctions across the LVV-affected hemispheres suggest additional stroke etiologies of vasculopathy (i.e., thromboembolism) in addition to chronic hypoxia-ischemia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Plasma volume and blood volume are imaging-derived parameters that are often used to evaluation intracranial tumors. Physiologically, these parameters are directly related, but their two different methods of measurements, T1-dynamic contrast enhanced (DCE)- and T2-dynamic susceptibility contrast (DSC)-MR utilize different model assumptions and approaches. This poses the question of whether the interchangeable use of T1-DCE-MRI derived fractionated plasma volume (vp) and relative cerebral blood volume (rCBV) assessed using DSC-MRI, particularly in glioblastoma, is reliable, and if this relationship can be generalized to other types of brain tumors. Our goal was to examine the hypothetical correlation between these parameters in three most common intracranial tumor types., Methods: Twenty-four newly diagnosed, treatment naïve brain tumor patients, who had undergone DCE- and DSC-MRI, were classified in three histologically proven groups: glioblastoma (n = 7), meningioma (n = 9), and intraparenchymal metastases (n = 8). The rCBV was obtained from DSC after normalization with the normal-appearing anatomically symmetrical contralateral white matter. Correlations between these parameters were evaluated using Pearson (r), Spearman's (ρ) and Kendall's tau-b (τB) rank correlation coefficient., Results: The Pearson, Spearman and Kendall's correlation between vp with rCBV were r = 0.193, ρ = 0.253 and τB = 0.33 (p-Pearson = 0.326, p-Spearman = 0.814 and p-Kendall = 0.823) in glioblastoma, r = -0.007, ρ = 0.051 and τB = 0.135 (p-Pearson = 0.970, p-Spearman = 0.765 and p-Kendall = 0.358) in meningiomas, and r = 0.289, ρ = 0.228 and τB = 0.239 (p-Pearson = 0.109, p-Spearman = 0.210 and p-Kendall = 0.095) in metastasis., Conclusion: Results indicate that no correlation exists between vp with rCBV in glioblastomas, meningiomas and intraparenchymal metastatic lesions. Consequently, these parameters, as calculated in this study, should not be used interchangeably in either research or clinical practice., Competing Interests: The authors have declared that no competing interests exist.

Purpose: A new T1 mapping method is proposed that is accurate, rapid, and robust to motion. Considering these features, the method is dubbed "T-One with Enhanced Robustness and Speed (TOWERS).", Methods: TOWERS is composed of inversion recovery (IR) and saturation recovery (SR) acquisitions. In the IR acquisitions, a slice reordering scheme is used to sample all slices in an efficient manner, whereas the SR acquisitions serve as references for motion estimation. Furthermore, as opposed to the usual way of running generalized autocalibrating partially parallel acquisitions (GRAPPA) calibration only once at the beginning, GRAPPA coefficients are updated in the middle and at the end, and are later used for retrospectively correcting for motion artifacts. Finally, sub-voxel magnetization tracking is deployed to account for motion-induced signal evolution changes., Results: Whole-brain T1 mapping data with a spatial resolution of 1.56 × 1.56 × 2.00 mm can be collected within 2.5 min. TOWERS and the gold-standard IR method agree well in phantom, while high reproducibility is achieved in vivo. High-quality T1 maps in the presence of severe motion show the robustness of the method., Conclusion: The proposed method, TOWERS, is shown to be rapid, accurate, and robust. Multiple GRAPPA calibrations and sub-voxel magnetization tracking make TOWERS unique. Magn Reson Med 76:118-126, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background and Purpose: We aimed to examine perfusion changes between 3 and 6 and 6 and 24 hours after stroke onset and their impact on tissue outcome., Methods: Acute ischemic stroke patients underwent perfusion magnetic resonance imaging at 3, 6, and 24 hours after stroke onset and follow-up fluid-attenuated inversion recovery at 1 month to assess tissue fate. Mean transit time prolongation maps (MTTp=MTT-[median MTT of contralateral hemisphere]) were obtained at 3 (MTTp3 h), 6 (MTTp6 h), and 24 hours (MTTp24 h). Perfusion changes between 3 and 6 hours (ΔMTTp3&#95;6) and 6 and 24 hours (ΔMTTp6&#95;24) were calculated. A 2-step analysis was performed to evaluate the impact of ΔMTTp3&#95;6 and ΔMTTp6&#95;24 on tissue fate. First, a voxel-based multivariable logistic regression was performed for each individual patient with MTTp3 h, ΔMTTp3&#95;6, and ΔMTT6&#95;24 as independent variables and tissue fate as outcome. Second, Wilcoxon signed-rank tests on logistic regression coefficients were performed across patients to evaluate whether ΔMTTp3&#95;6 and ΔMTT6&#95;24 had significant impact on tissue fate for varying severities of baseline perfusion., Results: Perfusion change was common during both time periods: 85% and 81% of patients had perfusion improvement during 3- to 6- and 6- and 24-hour time intervals, respectively. ΔMTT3&#95;6 significantly influenced 1-month infarct probability across a wide range of baseline perfusion (MTTp 0-15 s). ΔMTT6&#95;24 also impacted 1-month infarct probability, but its influence was restricted to tissue with milder baseline ischemia (MTTp 0-10 s)., Conclusions: Brain tissue with mild to moderate ischemia can be salvaged by reperfusion even after 6 hours. Such tissue could be targeted for intervention beyond current treatment windows., (© 2015 American Heart Association, Inc.)

Background and Purpose: Alterations of cerebral glucose metabolism are well anticipated during cerebral ischemia. However, detailed spatiotemporal characteristics of disturbed cerebral glucose metabolism during acute ischemia remain largely elusive. This study aims to delineate spatiotemporal distributions of [18]F-2-fluoro-2-deoxy-D-glucose (FDG) uptake using positron emission tomography imaging, particularly at the peri-ischemic zone, and its correlation with tissue outcome., Methods: The intraluminal suture middle cerebral artery occlusion model was used to induce focal cerebral ischemia in rats (n=48). All animals underwent sequential MRI and FDG positron emission tomography imaging at different times (30-150 minutes) after middle cerebral artery occlusion. MR and positron emission tomography images were coregistered. FDG uptake in the peri-ischemic zone was assessed in relation to middle cerebral artery occlusion duration, cerebral blood flow, apparent diffusion coefficient, and 24-hour T2 lesions., Results: Elevated FDG uptake was consistently observed at the peri-ischemic zone surrounding the presumed ischemic core with low FDG uptake. Both the spatial volume and the uptake level of the hyper-uptake region were inversely correlated with the duration of middle cerebral artery occlusion. The hyper-uptake regions exhibited a mild reduction of cerebral blood flow (28.2±3.2%) and apparent diffusion coefficient (9.1±1.4%) when compared with that in the contralateral hemisphere. Colocalization analysis revealed that, with reperfusion, an average of 12.1±1.7% of the hyper-uptake volume was recruited into final infarction., Conclusions: Elevated FDG uptake at the peri-ischemic zone is consistently observed during acute cerebral ischemia. The region with elevated FDG uptake likely reflects viable tissues that can be salvaged with reperfusion. Therefore, acute FDG positron emission tomography imaging might hold promise in the management of patients with acute stroke.

Cerebral oxygen metabolism plays a critical role in maintaining normal function of the brain. It is the primary energy source to sustain neuronal functions. Abnormalities in oxygen metabolism occur in various neuro-pathologic conditions such as ischemic stroke, cerebral trauma, cancer, Alzheimer's disease and shock. Therefore, the ability to quantitatively measure tissue oxygenation and oxygen metabolism is essential to the understanding of pathophysiology and treatment of various diseases. The focus of this review is to provide an introduction of various blood oxygenation level dependent (BOLD) contrast methods for absolute measurements of tissue oxygenation, including both magnitude and phase image based approaches. The advantages and disadvantages of each method are discussed.

Background and Purpose: it is hypothesized that tissue plasminogen activator rescues brain tissue by improving perfusion. In this study, we aimed to examine acute regional perfusion changes and how they influence infarction and clinical outcome., Methods: three sequential MR scans were performed in 15 tissue plasminogen activator-treated patients within 3.5 (tp1), at 6 hours (tp2), and at 1 month (tp3) after stroke onset. "Hypoperfusion" was defined if mean transit time prolongation was more than a threshold (4 thresholds: 3, 4, 5, and 6 seconds). Four regions of interest were classified: (1) "reperfusion"-hypoperfused at tp1, normal at tp2; (2) "nonreperfusion"-hypoperfused at tp1 and tp2; (3) "normal perfusion"-normal at tp1 and tp2; and (4) "new hypoperfusion"-normal at tp1 and hypoperfused at tp2. Risk of infarction was calculated within each region of interest. Associations between tissue perfusion changes and clinical variables were evaluated using stepwise multiple linear regressions. Moreover, the association between National Institutes of Health Stroke Scale changes and perfusion alterations was assessed using linear mixed effect models., Results: regardless of the mean transit time threshold chosen, the risk of infarction in nonreperfused regions (40% to 68%, thresholds 3 to 6 seconds) was higher than reperfused regions (9% to 30%, P<0.05), and it was higher in new hypoperfusion regions (9% to 33%) than normal perfusion regions (3% to 4%, P<0.05). Volume of new hypoperfusion was significantly associated with onset-to-treatment time and initial hypoperfused volume. Overall relative reperfusion was significantly associated with National Institutes of Health Stroke Scale improvement., Conclusions: early tissue perfusion changes influenced final tissue fate. The development of new hypoperfusion may result from delay in tissue plasminogen activator and a large initial lesion.

Many infrared optical systems in wide-ranging applications such as surveillance and security frequently require large fields of view (FOVs). Often this necessitates a focal plane array (FPA) with a large number of pixels, which, in general, is very expensive. In a previous paper, we proposed a method for increasing the FOV without increasing the pixel resolution of the FPA by superimposing multiple sub-images within a static scene and disambiguating the observed data to reconstruct the original scene. This technique, in effect, allows each sub-image of the scene to share a single FPA, thereby increasing the FOV without compromising resolution. In this paper, we demonstrate the increase of FOVs in a realistic setting by physically generating a superimposed video from a single scene using an optical system employing a beamsplitter and a movable mirror. Without prior knowledge of the contents of the scene, we are able to disambiguate the two sub-images, successfully capturing both large-scale features and fine details in each sub-image. We improve upon our previous reconstruction approach by allowing each sub-image to have slowly changing components, carefully exploiting correlations between sequential video frames to achieve small mean errors and to reduce run times. We show the effectiveness of this improved approach by reconstructing the constituent images of a surveillance camera video.