PHF19 before and post induction treatment possess favorable potency of reflecting treatment response to protease inhibitors, event-free survival, and overall survival in multiple myeloma patients.

OBJECTIVE: Plant homeodomain finger protein 19 (PHF19) regulates hematopoietic stem cell differentiation and promotes multiple myeloma (MM) progression. This study intended to explore the potency of PHF19 at baseline and post induction treatment in estimating treatment response to protease inhibitors and survival in MM patients. METHODS: This retrospective study screened 69 MM patients who received protease inhibitors with bone marrow (BM) samples available at both baseline and post induction treatment. Twenty healthy BM donors were included as healthy controls (HCs). PHF19 in plasma cells from BM was quantified by reverse transcription-quantitative polymerase chain reaction. RESULTS: PHF19 at baseline and post induction treatment in MM patients were increased than in HCs. In MM patients, PHF19 was declined post induction treatment. Elevated PHF19 at baseline and post induction treatment were correlated with renal impairment, beta-2-microglobulin ≥5.5 mg/L, t (4; 14), higher international staging system (ISS) stage, and higher revised ISS (R-ISS) stage. Concerning treatment response, PHF19 at baseline and post induction treatment were negatively associated with complete response and overall response rate. Notably, abnormal PHF19 (above 95% quantile value of PHF19 in HCs) at baseline and post induction treatment were linked with shortened event-free survival (EFS) and overall survival (OS). After adjustment, abnormal PHF19 post induction treatment was independently related to shortened EFS (hazard ratio = 2.474) and OS (hazard ratio = 3.124). CONCLUSION: PHF19 is aberrantly high and declines post induction therapy, which simultaneously reflects unfavorable treatment response to protease inhibitors as well as shorter EFS and OS in MM patients.

Technical note: Minimizing CIED artifacts on a 0.35 T MRI-Linac using deep learning.

BACKGROUND: Artifacts from implantable cardioverter defibrillators (ICDs) are a challenge to magnetic resonance imaging (MRI)-guided radiotherapy (MRgRT). PURPOSE: This study tested an unsupervised generative adversarial network to mitigate ICD artifacts in balanced steady-state free precession (bSSFP) cine MRIs and improve image quality and tracking performance for MRgRT. METHODS: Fourteen healthy volunteers (Group A) were scanned on a 0.35 T MRI-Linac with and without an MR conditional ICD taped to their left pectoral to simulate an implanted ICD. bSSFP MRI data from 12 of the volunteers were used to train a CycleGAN model to reduce ICD artifacts. The data from the remaining two volunteers were used for testing. In addition, the dataset was reorganized three times using a Leave-One-Out scheme. Tracking metrics [Dice similarity coefficient (DSC), target registration error (TRE), and 95 percentile Hausdorff distance (95% HD)] were evaluated for whole-heart contours. Image quality metrics [normalized root mean square error (nRMSE), peak signal-to-noise ratio (PSNR), and multiscale structural similarity (MS-SSIM) scores] were evaluated. The technique was also tested qualitatively on three additional ICD datasets (Group B) including a patient with an implanted ICD. RESULTS: For the whole-heart contour with CycleGAN reconstruction: 1) Mean DSC rose from 0.910 to 0.935; 2) Mean TRE dropped from 4.488 to 2.877 mm; and 3) Mean 95% HD dropped from 10.236 to 7.700 mm. For the whole-body slice with CycleGAN reconstruction: 1) Mean nRMSE dropped from 0.644 to 0.420; 2) Mean MS-SSIM rose from 0.779 to 0.819; and 3) Mean PSNR rose from 18.744 to 22.368. The three Group B datasets evaluated qualitatively displayed a reduction in ICD artifacts in the heart. CONCLUSION: CycleGAN-generated reconstructions significantly improved both tracking and image quality metrics when used to mitigate artifacts from ICDs.

Respiratory motion management using a single rapid MRI scan for a 0.35 T MRI-Linac system.

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.

Normalization of cerebral hemodynamics after hematopoietic stem cell transplant in children with sickle cell disease.

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.

MR-assisted PET respiratory motion correction using deep-learning based short-scan motion fields.

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 (MoCo2000 , 5-6 min acquisition time) using a Fourier transform reconstruction or 200 spokes (MoCoP2P200 , 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 (SUVmax , SUVpeak , SUVmean , 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 MoCo2000 and MoCoP2P200 PET images had significantly higher SUVmax , SUVpeak , SUVmean and significantly lower lesion volume than non-motion-corrected (non-MoCo) PET images. There was no statistical difference between MoCo2000 and MoCoP2P200 PET images for SUVmax , SUVpeak , SUVmean or lesion volume. Both radiological reviewers found that MoCo2000 and MoCoP2P200 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.

IER3 (IEX-1) dysregulation serves as a potential prognostic factor in acute myeloid leukemia patients.

INTRODUCTION: Immediate early response 3 (IER3) has association with hematological malignancies' risk and prognosis, such as myelodysplastic syndrome, while its relation to acute myeloid leukemia (AML) is not clear. This study aimed to explore the correlation of IER3 with AML risk, clinical characteristics, complete remission (CR), event-free survival (EFS), and overall survival (OS). METHODS: A total of 93 de novo AML patients were included in this study. In addition, 30 patients with non-hyperplasia hematologic malignancies requiring bone marrow testing (as disease controls) and 30 health donors (as health controls) were also recruited. Bone morrow samples of AML patients (before treatment), disease controls (before treatment), and health controls (at donation) were collected. IER3 in bone marrow mononuclear cells was detected by reverse transcription-quantitative polymerase chain reaction. RESULTS: IER3 was increased in AML patients compared with disease controls and health donors (both P < .001), and receiver operating characteristic (ROC) curve showed that IER3 had certain capability of distinguishing AML patients from disease controls (area under curve (AUC): 0.735, 95% confidence interval (CI): 0.650-0.820), and health donors (AUC: 0.789, 95% CI: 0.712-0.866). Meanwhile, IER3 was correlated with FLT3-ITD mutation (P = .030) and poor NCCN risk stratification (P = .031) in AML patients. Moreover, IER3 had negative association with CR in AML patients (P = .022), and showed certain potential in discriminating CR patients from non-CR patients (AUC: 0.655, 95% CI: 0.533-0.777). Besides, IER3 was negatively associated with EFS (P = .033), but not OS (P = .083) in AML patients. CONCLUSION: IER3 dysregulation serves as a potential prognostic factor in AML patients.

Reduction in cerebral oxygen metabolism in subcortical regions may be a biomarker of cognitive decline in people living with human immunodeficiency virus.

BACKGROUND AND PURPOSE: Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2 ) in whole brain, white matter, gray matter and lenticular nuclei were studied in people living with human immunodeficiency virus (PLHIV) as well as HIV-associated neurocognitive disorder (HAND). METHODS: Treatment-naïve PLHIV underwent neurocognitive assessment and magnetic resonance (MR) measurement of rCBF and rCMRO2 with repeat after 12 months of antiretroviral therapy (ART). Age- and sex-matched controls underwent single MR measurements. Regional CBF and rCMRO2 were compared amongst symptomatic, asymptomatic, normal HAND and controls using analysis of variance. Longitudinal analysis of HAND worsening (≥1 category) was assessed after 12 months of ART and correlated with rCBF and rCMRO2 measured by MR imaging using the paired-sample t test. RESULTS: Thirty PLHIV completed baseline and 12-month assessments (29 with rCMRO2 measurement). At baseline HAND assessment, 13% had no cognitive impairment, 27% had asymptomatic neurocognitive impairment, 60% had mild neurocognitive disorder and none had HIV-associated dementia. At 12 months, 13% had no cognitive impairment, 20% had asymptomatic neurocognitive impairment, 50% had mild neurocognitive disorder and 17% had HIV-associated dementia. In those without HAND worsening (N = 21) rCMRO2 remained stable and in those with HAND worsening (N = 8) rCMRO2 measurement declined from baseline to 12 months in white matter (2.05 ± 0.40 to 1.73 ± 0.51, p = 0.03) and lenticular nuclei (4.32 ± 0.39 to 4.00 ± 0.51, p = 0.05). CONCLUSIONS: In recently diagnosed PLHIV, no association was found between rCBF or rCMRO2 and cognitive impairment at baseline. There was a reduction in rCMRO2 in those with worsening of cognitive function at 12 months on ART. Reduction in rCMRO2 may be a biomarker of cognitive decline in PLHIV.

ITGA7 relates to disease risk, pathological feature, treatment response and survival in Ph- acute lymphoblastic leukemia.

Background: This study aimed to investigate clinical involvement of ITGA7 in Philadelphia-chromosome-negative acute lymphoblastic leukemia (Ph- ALL). Methods: We sampled bone marrow (BM) from 91 Ph- ALL patients and 20 healthy donors (HDs), detecting ITGA7 expression in BM. Results: ITGA7 was highly expressed in Ph- ALL patients at differentiating values between Ph- ALL patients and HDs. Elevated ITGA7 expression was associated with CNS leukemia (CNSL) occurrence and increased percentage of BM blasts in Ph- ALL patients. Elevated ITGA7 expression was linked with lower complete remission rate (CR), worse event-free survival, and worse overall survival in Ph- ALL patients. Conclusion: ITGA7 highly expressed, correlated with CNSL occurrence and higher BM blasts, furthermore predicts lower CR rate and worse prognosis.

Phase2Phase: Respiratory Motion-Resolved Reconstruction of Free-Breathing Magnetic Resonance Imaging Using Deep Learning Without a Ground Truth for Improved Liver Imaging.

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.

Transcriptome and lipidome profile of human mesenchymal stem cells with reduced senescence and increased trilineage differentiation ability upon drug treatment.

Human Mesenchymal stem cells (hMSCs) are multi-potential cells which are widely used in cell therapy. However, the frequently emerged senescence and decrease of differentiation capabilities limited the broad applications of MSC. Several strategies such as small molecules treatment have been widely studied and used to improve the stem characteristics bypassing the senescence but the exact mechanisms for them to reduce senescence have not been fully studied. In this study, hMSCs were treated by rapamycin, oltipraz, metformin, and vitamin C for the indicated time and these cells were subjected to senescence evaluation and trilineage differentiation. Furthermore, transcriptomics and lipidomics datasets of hMSCs after drug treatment were analyzed to interpret biological pathways responsible for their anti-senescence effects. Although four drugs exhibited significant activities in promoting MSC osteogenic differentiation, metformin is the optimal drug to promote trilineage differentiation. GO terms illustrated that the anti-aging effects of drugs were mainly associated with cellular senescence, mitotic and meiosis process. Biosynthesis of phosphatidylcholines (PC) and phosphatidylethanolamine (PE) were inhibited whereas production of phosphatidylinositols (PIs) and saturated fatty acids (SFA)/ mono-unsaturated fatty acids (MUFA) conversion was activated. Medium free fatty acids (FFA) was increased in hMSCs with different anti-aging phenotypes. Therefore, we established a comprehensive method in assessing drug intervention based on the results of transcriptomics and lipidomics. The method can be used to study different biological phenotypes upon drug intervention in MSC which will extend the clinical application of hMSCs.

Optimal co-clinical radiomics: Sensitivity of radiomic features to tumour volume, image noise and resolution in co-clinical T1-weighted and T2-weighted magnetic resonance imaging.

BACKGROUND: Radiomics analyses has been proposed to interrogate the biology of tumour as well as to predict/assess response to therapy in vivo. The objective of this work was to assess the sensitivity of radiomics features to noise, resolution, and tumour volume in the context of a co-clinical trial. METHODS: Triple negative breast cancer (TNBC) patients were recruited into an ongoing co-clinical imaging trial. Sub-typed matched TNBC patient-derived tumour xenografts (PDX) were generated to investigate optimal co-clinical MR radiomic features. The MR imaging protocol included T1-weighed and T2-weighted imaging. To test the sensitivity of radiomics to resolution, PDX were imaged at three different resolutions. Multiple sets of images with varying signal-to-noise ratio (SNR) were generated, and an image independent patch-based method was implemented to measure the noise levels. Forty-eight radiomic features were extracted from manually segmented 2D and 3D segmented tumours and normal tissues of T1- and T2- weighted co-clinical MR images. FINDINGS: Sixteen radiomics features were identified as volume dependent and corrected for volume-dependency following normalization. Features from grey-level run-length matrix (GLRLM), grey-level size zone matrix (GLSZM) were identified as most sensitive to noise. Radiomic features Kurtosis and Run-length variance (RLV) from GLSZM were most sensitive to changes in resolution in both T1w and T2w MRI. In general, 3D radiomic features were more robust compared to 2D (single slice) measures, although the former exhibited higher variability between subjects. INTERPRETATION: Tumour volume, noise characteristics, and image resolution significantly impact radiomic analysis in co-clinical studies.

Quantification of brain oxygen extraction and metabolism with [15O]-gas PET: A technical review in the era of PET/MRI.

Oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2) are key cerebral physiological parameters to identify at-risk cerebrovascular patients and understand brain health and function. PET imaging with [15O]-oxygen tracers, either through continuous or bolus inhalation, provides non-invasive assessment of OEF and CMRO2. Numerous tracer delivery, PET acquisition, and kinetic modeling approaches have been adopted to map brain oxygenation. The purpose of this technical review is to critically evaluate different methods for [15O]-gas PET and its impact on the accuracy and reproducibility of OEF and CMRO2 measurements. We perform a meta-analysis of brain oxygenation PET studies in healthy volunteers and compare between continuous and bolus inhalation techniques. We also describe OEF metrics that have been used to detect hemodynamic impairment in cerebrovascular disease. For these patients, advanced techniques to accelerate the PET scans and potential synthesis with MRI to avoid arterial blood sampling would facilitate broader use of [15O]-oxygen PET for brain physiological assessment.

Evaluating the Use of rCBV as a Tumor Grade and Treatment Response Classifier Across NCI Quantitative Imaging Network Sites: Part II of the DSC-MRI Digital Reference Object (DRO) Challenge.

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.

Evaluating Multisite rCBV Consistency from DSC-MRI Imaging Protocols and Postprocessing Software Across the NCI Quantitative Imaging Network Sites Using a Digital Reference Object (DRO).

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).

Measurement Repeatability of 18F-FDG PET/CT Versus 18F-FDG PET/MRI in Solid Tumors of the Pelvis.

Knowledge of the within-subject variability of 18F-FDG PET/MRI measurements is necessary for proper interpretation of quantitative PET or MRI metrics in the context of therapeutic efficacy assessments with integrated PET/MRI scanners. The goal of this study was to determine the test-retest repeatability of these metrics on PET/MRI, with comparison to similar metrics acquired by PET/CT. Methods: This prospective study enrolled subjects with pathology-proven pelvic malignancies. Baseline imaging consisted of PET/CT immediately followed by PET/MRI, using a single 370-MBq 18F-FDG dose. Repeat imaging was performed within 7 d using an identical imaging protocol, with no oncologic therapy between sessions. PET imaging on both scanners consisted of a list-mode acquisition at a single pelvic station. The MRI consisted of 2-point Dixon imaging for attenuation correction, standard sequences for anatomic correlation, and diffusion-weighted imaging. PET data were statically reconstructed using various frame durations and minimizing uptake time differences between sessions. SUV metrics were extracted for both PET/CT and PET/MRI in each imaging session. Apparent diffusion coefficient (ADC) metrics were extracted for both PET/MRI sessions. Results: The study cohort consisted of 14 subjects (13 female, 1 male) with various pelvic cancers (11 cervical, 2 rectal, 1 endometrial). For SUVmax, the within-subject coefficient of variation (wCV) appeared higher for PET/CT (8.5%-12.8%) than PET/MRI (6.6%-8.7%) across all PET reconstructions, though with no significant repeatability differences (all P values ≥ 0.08) between modalities. For lean body mass-adjusted SUVpeak, the wCVs appeared similar for PET/CT (9.9%-11.5%) and PET/MRI (9.2%-11.3%) across all PET reconstructions, again with no significant repeatability differences (all P values ≥ 0.14) between modalities. For PET/MRI, the wCV for ADCmedian of 3.5% appeared lower than the wCVs for SUVmax (6.6%-8.7%) and SULpeak (9.2%-11.3%), though without significant repeatability differences (all P values ≥ 0.23). Conclusion: For solid tumors of the pelvis, the repeatability of the evaluated SUV and ADC metrics on 18F-FDG PET/MRI is both acceptably high and similar to previously published values for 18F-FDG PET/CT and MRI, supporting the use of 18F-FDG PET/MRI for quantitative oncologic treatment response assessments.

Application of Machine Learning to Automated Analysis of Cerebral Edema in Large Cohorts of Ischemic Stroke Patients.

Cerebral edema contributes to neurological deterioration and death after hemispheric stroke but there remains no effective means of preventing or accurately predicting its occurrence. Big data approaches may provide insights into the biologic variability and genetic contributions to severity and time course of cerebral edema. These methods require quantitative analyses of edema severity across large cohorts of stroke patients. We have proposed that changes in cerebrospinal fluid (CSF) volume over time may represent a sensitive and dynamic marker of edema progression that can be measured from routinely available CT scans. To facilitate and scale up such approaches we have created a machine learning algorithm capable of segmenting and measuring CSF volume from serial CT scans of stroke patients. We now present results of our preliminary processing pipeline that was able to efficiently extract CSF volumetrics from an initial cohort of 155 subjects enrolled in a prospective longitudinal stroke study. We demonstrate a high degree of reproducibility in total cranial volume registration between scans (R = 0.982) as well as a strong correlation of baseline CSF volume and patient age (as a surrogate of brain atrophy, R = 0.725). Reduction in CSF volume from baseline to final CT was correlated with infarct volume (R = 0.715) and degree of midline shift (quadratic model, p < 2.2 × 10-16). We utilized generalized estimating equations (GEE) to model CSF volumes over time (using linear and quadratic terms), adjusting for age. This model demonstrated that CSF volume decreases over time (p < 2.2 × 10-13) and is lower in those with cerebral edema (p = 0.0004). We are now fully automating this pipeline to allow rapid analysis of even larger cohorts of stroke patients from multiple sites using an XNAT (eXtensible Neuroimaging Archive Toolkit) platform. Data on kinetics of edema across thousands of patients will facilitate precision approaches to prediction of malignant edema as well as modeling of variability and further understanding of genetic variants that influence edema severity.

CAPTURE: Consistently Acquired Projections for Tuned and Robust Estimation: A Self-Navigated Respiratory Motion Correction Approach.

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.

Large-Vessel Vasculopathy in Children With Sickle Cell Disease: A Magnetic Resonance Imaging Study of Infarct Topography and Focal Atrophy.

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.

Comparison of Cerebral Blood Volume and Plasma Volume in Untreated Intracranial Tumors.

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.

CSF Volumetric Analysis for Quantification of Cerebral Edema After Hemispheric Infarction.

BACKGROUND: Malignant cerebral edema (CED) complicates at least 20 % of large hemispheric infarcts (LHI) and may result in neurological deterioration or death. Midline shift (MLS) is a standard but crude measure of edema severity. We propose that volumetric analysis of shifts in cerebrospinal fluid (CSF) over time provides a reliable means of quantifying the spectrum of edema severity after LHI. METHODS: We identified 38 patients from 2008 to 2014 with NIHSS ≥8, baseline CT <6 h after stroke onset, at least 1 follow-up (FU) CT, and no parenchymal hematoma. The volumes of CSF (sulci, ventricles, and cisterns) ipsilateral (IL) and contralateral (CL) to infarct on baseline and FU CTs were quantified by manually assisted outlining with MIPAV image analysis software, as was infarct volume and MLS on FU CTs. Percentage change in CSF volumes (∆CSF) from baseline to FU scans was correlated with MLS and compared in those with vs. without malignant edema (defined as hemicraniectomy, osmotic therapy, or death/neurological deterioration with MLS ≥5 mm). RESULTS: 11 of 38 subjects (29 %) developed malignant edema. Neither baseline NIHSS nor CSF volume differed between those with and without edema (median NIHSS 18 vs. 13, p = 0.12, CSF volume 102 vs. 124 ml, p = 0.16). Inter-rater reliability for CSF measurements was excellent (intraclass correlation coefficient 0.97). ∆CSF correlated strongly with MLS at peak edema (r = -0.75), even adjusting for infarct volume (p = 0.009). ∆CSF was also greater in those with malignant edema [-55 % (IQR -49 to -62) vs. -36 % (-27 to -45), p = 0.004]. ∆CSF was the greatest within IL sulci [-97 % (-86 to -99) vs. -71 % (-41 to -79), p = 0.002] but also significantly greater within CL sulci in those with malignant edema [-50 % (-29 to -65) vs. -25 % (0 to -31), p = 0.014]. More than half this CSF volume reduction occurred by the time of first FU CT around 24 h after stroke, while MLS rose later. CONCLUSIONS: Volumetric CSF analysis reliably quantifies CED and distinguishes those with malignant edema and MLS from those with a more benign course after LHI. ∆CSF may provide an earlier and more sensitive indicator of edema severity across a broader dynamic range than MLS.