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PurposeTo develop an MR multitasking-based multidimensional assessment of cardiovascular system (MT-MACS) with electrocardiography-free and navigator-free data acquisition for a comprehensive evaluation of thoracic aortic diseases.MethodsThe MT-MACS technique adopts a low-rank tensor image model with a cardiac time dimension for phase-resolved cine imaging and a T2 -prepared inversion-recovery dimension for multicontrast assessment. Twelve healthy subjects and 2 patients with thoracic aortic diseases were recruited for the study at 3 T, and both qualitative (image quality score) and quantitative (contrast-to-noise ratio between lumen and wall, lumen and wall area, and aortic strain index) analyses were performed in all healthy subjects. The overall image quality was scored based on a 4-point scale: 3, excellent; 2, good; 1, fair; and 0, poor. Statistical analysis was used to test the measurement agreement between MT-MACS and its corresponding 2D references.ResultsThe MT-MACS images reconstructed from acquisitions as short as 6 minutes demonstrated good or excellent image quality for bright-blood (2.58 ± 0.46), dark-blood (2.58 ± 0.50), and gray-blood (2.17 ± 0.53) contrast weightings, respectively. The contrast-to-noise ratios for the three weightings were 49.2 ± 12.8, 20.0 ± 5.8 and 2.8 ± 1.8, respectively. There were good agreements in the lumen and wall area (intraclass correlation coefficient = 0.993, P < .001 for lumen; intraclass correlation coefficient = 0.969, P < .001 for wall area) and strain (intraclass correlation coefficient = 0.947, P < .001) between MT-MACS and conventional 2D sequences.ConclusionThe MT-MACS technique provides high-quality, multidimensional images for a comprehensive assessment of the thoracic aorta. Technical feasibility was demonstrated in healthy subjects and patients with thoracic aortic diseases. Further clinical validation is warranted.

PurposeSegmentation of multiple organs-at-risk (OARs) is essential for magnetic resonance (MR)-only radiation therapy treatment planning and MR-guided adaptive radiotherapy of abdominal cancers. Current practice requires manual delineation that is labor-intensive, time-consuming, and prone to intra- and interobserver variations. We developed a deep learning (DL) technique for fully automated segmentation of multiple OARs on clinical abdominal MR images with high accuracy, reliability, and efficiency.MethodsWe developed Automated deep Learning-based abdominal multiorgan segmentation (ALAMO) technique based on two-dimensional U-net and a densely connected network structure with tailored design in data augmentation and training procedures such as deep connection, auxiliary supervision, and multiview. The model takes in multislice MR images and generates the output of segmentation results. 3.0-Tesla T1 VIBE (Volumetric Interpolated Breath-hold Examination) images of 102 subjects were used in our study and split into 66 for training, 16 for validation, and 20 for testing. Ten OARs were studied, including the liver, spleen, pancreas, left/right kidneys, stomach, duodenum, small intestine, spinal cord, and vertebral bodies. An experienced radiologist manually labeled each OAR, followed by reediting, if necessary, by a senior radiologist, to create the ground-truth. The performance was measured using volume overlapping and surface distance.ResultsThe ALAMO technique generated segmentation labels in good agreement with the manual results. Specifically, among the ten OARs, nine achieved high dice similarity coefficients (DSCs) in the range of 0.87-0.96, except for the duodenum with a DSC of 0.80. The inference completed within 1 min for a three-dimensional volume of 320 × 288 × 180. Overall, the ALAMO model matched the state-of-the-art techniques in performance.ConclusionThe proposed ALAMO technique allows for fully automated abdominal MR segmentation with high accuracy and practical memory and computation time demands.

PurposeTo develop a quantitative DCE MRI technique enabling entire-abdomen coverage, free-breathing acquisition, 1-second temporal resolution, and T1 -based quantification of contrast agent concentration and kinetic modeling for the characterization of pancreatic ductal adenocarcinoma (PDAC).MethodsSegmented FLASH readouts following saturation-recovery preparation with randomized 3D Cartesian undersampling was used for incoherent data acquisition. MR Multitasking was used to reconstruct 6-dimensional images with 3 spatial dimensions, 1 T1 recovery dimension for dynamic T1 quantification, 1 respiratory dimension to resolve respiratory motion, and 1 DCE time dimension to capture the contrast kinetics. Sixteen healthy subjects and 14 patients with pathologically confirmed PDAC were recruited for the in vivo studies, and kinetic parameters vp , Ktrans , ve , and Kep were evaluated for each subject. Intersession repeatability of Multitasking DCE was assessed in 8 repeat healthy subjects. One-way unbalanced analysis of variance was performed between control and patient groups.ResultsIn vivo studies demonstrated that vp , Ktrans , and Kep of PDAC were significantly lower compared with nontumoral regions in the patient group (P = .002, .003, .004, respectively) and normal pancreas in the control group (P = .011,

PurposeTo develop a simultaneous T1 , T2 , and ADC mapping method that provides co-registered, distortion-free images and enables multiparametric quantification of 3D brain coverage in a clinically feasible scan time with the MR Multitasking framework.MethodsThe T1 /T2 /diffusion weighting was generated by a series of T2 preparations and diffusion preparations. The underlying multidimensional image containing 3 spatial dimensions, 1 T1 weighting dimension, 1 T2 -preparation duration dimension, 1 b-value dimension, and 1 diffusion direction dimension was modeled as a 5-way low-rank tensor. A separate real-time low-rank model incorporating time-resolved phase correction was also used to compensate for both inter-shot and intra-shot phase inconsistency induced by physiological motion. The proposed method was validated on both phantom and 16 healthy subjects. The quantification of T1 /T2 /ADC was evaluated for each case. Three post-surgery brain tumor patients were scanned for demonstration of clinical feasibility.ResultsMultitasking T1 /T2 /ADC maps were perfectly co-registered and free from image distortion. Phantom studies showed substantial quantitative agreement ( R2=0.999 ) with reference protocols for T1 /T2 /ADC. In vivo studies showed nonsignificant T1 (P = .248), T2 (P = .97), ADC (P = .328) differences among the frontal, parietal, and occipital regions. Although Multitasking showed significant differences of T1 (P = .03), T2 (P < .001), and ADC (P = .001) biases against the references, the mean bias estimates were small (ΔT1 % < 5%, ΔT2 % < 7%, ΔADC% < 5%), with all intraclass correlation coefficients greater than 0.82 indicating "excellent" agreement. Patient studies showed that Multitasking T1 /T2 /ADC maps were consistent with the clinical qualitative images.ConclusionThe Multitasking approach simultaneously quantifies T1 /T2 /ADC with substantial agreement with the references and is promising for clinical applications.

BackgroundCurrent magnetic resonance imaging (MRI) of pancreatic disease is qualitative in nature. Quantitative imaging offers several advantages, including increased reproducibility and sensitivity to detect mild or diffuse disease. The role of multiparametric mapping MRI in characterizing various tissue types in pancreatic disease such as chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) has rarely been evaluated.PurposeTo evaluate the feasibility of multiparametric mapping [T1, T2, and apparent diffusion coefficient (ADC)] in defining tissue characteristics that occur in CP and PDAC to improve disease diagnosis.Materials and methodsPancreatic MRI was performed in 17 patients with PDAC undergoing therapy, 7 patients with CP, and 29 healthy volunteers with no pancreatic disease. T1 modified Look-Locker Inversion Recovery (T1 MOLLI), T2-prepared gradient-echo, and multi-slice single-shot echo-planar diffusion weighted imaging (SS-EPI DWI) sequences were used for data acquisition. Regions of interest (ROIs) of pancreas in PDAC, CP, and control subjects were outlined by an experienced radiologist. One-way analysis of variance (ANOVA) was used to compare the difference between groups and regions of the pancreas, and Tukey tests were used for multiple comparison testing within groups. Receiver operator characteristic (ROC) curves were analyzed, and the areas under the curves (AUCs) were calculated using single parameter and combined parameters, respectively.ResultsT1, T2, and ADC values of the entire pancreas among PDAC, CP, and control subjects; and between upstream and downstream portions of the pancreas in PDAC patients were all significantly different (p < 0.05). The AUC values were 0.90 for T1, 0.55 for T2, and 0.71 for ADC for independent prediction of PDAC. By combining T1, T2, and ADC, the AUC value was 0.94 (sensitivity 91.54%, specificity 85.81%, 95% CI: 0.92-0.96), which yielded higher accuracy than any one parameter only (p < 0.001).ConclusionMultiparametric mapping MRI is feasible for the evaluation of the differences between PDAC, CP, and normal pancreas tissues. The combination of multiple parameters of T1, T2, and ADC provides a higher accuracy than any single parameter alone in tissue characterization of the pancreas.

PurposeTo evaluate the accuracy and repeatability of a free-breathing, non-electrocardiogram (ECG), continuous myocardial T1 and extracellular volume (ECV) mapping technique adapted from the Multitasking framework.MethodsThe Multitasking framework is adapted to quantify both myocardial native T1 and ECV with a free-breathing, non-ECG, continuous acquisition T1 mapping method. We acquire interleaved high-spatial resolution image data and high-temporal resolution auxiliary data following inversion-recovery pulses at set intervals and perform low-rank tensor imaging to reconstruct images at 344 inversion times, 20 cardiac phases, and 6 respiratory phases. The accuracy and repeatability of Multitasking T1 mapping in generating native T1 and ECV maps are compared with conventional techniques in a phantom, a simulation, 12 healthy subjects, and 10 acute myocardial infarction patients.ResultsIn phantoms, Multitasking T1 mapping correlated strongly with the gold-standard spin-echo inversion recovery (R2 = 0.99). A simulation study demonstrated that Multitasking T1 mapping has similar myocardial sharpness to the fully sampled ground truth. In vivo native T1 and ECV values from Multitasking T1 mapping agree well with conventional MOLLI values and show good repeatability for native T1 and ECV mapping for 60 seconds, 30 seconds, or 15 seconds of data. Multitasking native T1 and ECV in myocardial infarction patients correlate positively with values from MOLLI.ConclusionMultitasking T1 mapping can quantify native T1 and ECV in the myocardium with free-breathing, non-ECG, continuous scans with good image quality and good repeatability in vivo in healthy subjects, and correlation with MOLLI T1 and ECV in acute myocardial infarction patients.

PurposeTo develop a dynamic contrast-enhanced (DCE) MRI method capable of high spatiotemporal resolution, 3D carotid coverage, and T1-based quantification of contrast agent concentration for the assessment of carotid atherosclerosis using a newly developed Multitasking technique.Methods5D imaging with 3 spatial dimensions, 1 T1 recovery dimension, and 1 DCE time dimension was performed using MR Multitasking based on low-rank tensor modeling, which allows direct T1 quantification with high spatiotemporal resolution (0.7 mm isotropic and 595 ms, respectively). Saturation recovery preparations followed by 3D segmented fast low angle shot readouts were implemented with Gaussian-density random 3D Cartesian sampling. A bulk motion removal scheme was developed to improve image quality. The proposed protocol was tested in phantom and human studies. In vivo scans were performed on 14 healthy subjects and 7 patients with carotid atherosclerosis. Kinetic parameters including area under the concentration versus time curve (AUC), vp , Ktrans , and ve were evaluated for each case.ResultsPhantom experiments showed that T1 measurements using the proposed protocol were in good agreement with reference value ( R 2 = 0.96 ). In vivo studies demonstrated that AUC, vp , and Ktrans in the patient group were significantly higher than in the control group (0.63 ± 0.13 versus 0.42 ± 0.12, P < 0.001; 0.14 ± 0.05 versus 0.11 ± 0.03, P = 0.034; and 0.13 ± 0.04 versus 0.08 ± 0.02, P < 0.001, respectively). Results from repeated subjects showed good interscan reproducibility (intraclass correlation coefficient: vp , 0.83; Ktrans , 0.87; ve , 0.92; AUC, 0.94).ConclusionMultitasking DCE is a promising approach for quantitatively assessing the vascularity properties of the carotid vessel wall.

There is an unmet need for the treatment of glioblastoma multiforme (GBM). The extracellular matrix, including laminins, in the tumor microenvironment is important for tumor invasion and progression. In a panel of 226 patient brain glioma samples, we found a clinical correlation between the expression of tumor vascular laminin-411 (α4β1γ1) with higher tumor grade and with expression of cancer stem cell (CSC) markers, including Notch pathway members, CD133, Nestin, and c-Myc. Laminin-411 overexpression also correlated with higher recurrence rate and shorter survival of GBM patients. We also showed that depletion of laminin-411 α4 and β1 chains with CRISPR/Cas9 in human GBM cells led to reduced growth of resultant intracranial tumors in mice and significantly increased survival of host animals compared with mice with untreated cells. Inhibition of laminin-411 suppressed Notch pathway in normal and malignant human brain cell types. A nanobioconjugate potentially suitable for clinical use and capable of crossing blood-brain barrier was designed to block laminin-411 expression. Nanobioconjugate treatment of mice carrying intracranial GBM significantly increased animal survival and inhibited multiple CSC markers, including the Notch axis. This study describes an efficient strategy for GBM treatment via targeting a critical component of the tumor microenvironment largely independent of heterogeneous genetic mutations in glioblastoma.Significance: Laminin-411 expression in the glioma microenvironment correlates with Notch and other cancer stem cell markers and can be targeted by a novel, clinically translatable nanobioconjugate to inhibit glioma growth.

Methods:Nine patients (seven pancreas, one liver, and one lung) were recruited. 4D-MRI was performed using two prototype k-space sorted techniques, stack-of-stars (SOS) and koosh-ball (KB) acquisitions. Post-processing using MoCoAve was implemented for both methods. Image quality score, apparent SNR (aSNR), sharpness, motion trajectory and standard deviation (σ_GTV) of the gross tumor volumes were compared between original and MoCoAve image sets.Results:All subjects successfully underwent 4D-MRI scans and MoCoAve was performed on all data sets. Significantly higher image quality scores (2.64 ± 0.39 vs 1.18 ± 0.34, p = 0.001) and aSNR (37.6 ± 15.3 vs 18.1 ± 5.7, p = 0.001) was observed in the MoCoAve images when compared to the original images. High correlation in tumor motion trajectories in the superoinferior direction (SI: 0.91 ± 0.08) and weaker in the anteroposterior (AP: 0.51 ± 0.44) and mediolateral (ML: 0.37 ± 0.23) directions, similar image sharpness (0.367 ± 0.068 vs 0.369 ± 0.072, p = 0.805), and minimal average absolute difference (0.47 ± 0.34  mm) of the motion trajectory profiles was found between the two image sets. The σ_GTV in pancreas patients was significantly (p = 0.039) lower in MoCoAve images (1.48 ± 1.35  cm3) than in the original images (2.17 ± 1.31  cm3).Conclusion:MoCoAve using interphase motion correction and averaging has shown promise as a post-processing method for improving k-space sorted (SOS and KB) 4D-MRI image quality in thoracic and abdominal cancer patients.Advances in knowledge:The proposed method is an image based post-processing method that could be applied to many k-space sorted 4D-MRI methods for improved image quality and signal-to-noise ratio while preserving image sharpness and respiratory motion fidelity. It is a useful technique for the radiotherapy planning community who are interested in using 4D-MRI but aren't satisfied with their current MR image quality.

Purpose: To shorten CEST acquisition time by leveraging Z‐spectrum undersampling combined with deep learning for CEST map construction from undersampled Z‐spectra. Methods: Fisher information gain analysis identified optimal frequency offsets (termed "Fisher offsets") for the multi‐pool fitting model, maximizing information gain for the amplitude and the FWHM parameters. These offsets guided initial subsampling levels. A U‐NET, trained on undersampled brain CEST images from 18 volunteers, produced CEST maps at 3 T with varied undersampling levels. Feasibility was first tested using retrospective undersampling at three levels, followed by prospective in vivo undersampling (15 of 53 offsets), reducing scan time significantly. Additionally, glioblastoma grade IV pathology was simulated to evaluate network performance in patient‐like cases. Results: Traditional multi‐pool models failed to quantify CEST maps from undersampled images (structural similarity index [SSIM] <0.2, peak SNR <20, Pearson r <0.1). Conversely, U‐NET fitting successfully addressed undersampled data challenges. The study suggests CEST scan time reduction is feasible by undersampling 15, 25, or 35 of 53 Z‐spectrum offsets. Prospective undersampling cut scan time by 3.5 times, with a maximum mean squared error of 4.4e–4, r = 0.82, and SSIM = 0.84, compared to the ground truth. The network also reliably predicted CEST values for simulated glioblastoma pathology. Conclusion: The U‐NET architecture effectively quantifies CEST maps from undersampled Z‐spectra at various undersampling levels. [ABSTRACT FROM AUTHOR]

Purpose: Radiotherapy treatment planning (RTP) using MR has been used increasingly for the abdominal site. Multiple contrast weightings and motion‐resolved imaging are desired for accurate delineation of the target and various organs‐at‐risk and patient‐tailored planning. Current MR protocols achieve these through multiple scans with distinct contrast and variable respiratory motion management strategies and acquisition parameters, leading to a complex and inaccurate planning process. This study presents a standalone MR Multitasking (MT)–based technique to produce volumetric, motion‐resolved, multicontrast images for abdominal radiotherapy treatment planning. Methods: The MT technique resolves motion and provides a wide range of contrast weightings by repeating a magnetization‐prepared (saturation recovery and T2 preparations) spoiled gradient‐echo readout series and adopting the MT image reconstruction framework. The performance of the technique was assessed through digital phantom simulations and in vivo studies of both healthy volunteers and patients with liver tumors. Results: In the digital phantom study, the MT technique presented structural details and motion in excellent agreement with the digital ground truth. The in vivo studies showed that the motion range was highly correlated (R2 = 0.82) between MT and 2D cine imaging. MT allowed for a flexible contrast‐weighting selection for better visualization. Initial clinical testing with interobserver analysis demonstrated acceptable target delineation quality (Dice coefficient = 0.85 ± 0.05, Hausdorff distance = 3.3 ± 0.72 mm). Conclusion: The developed MT‐based, abdomen‐dedicated technique is capable of providing motion‐resolved, multicontrast volumetric images in a single scan, which may facilitate abdominal radiotherapy treatment planning. [ABSTRACT FROM AUTHOR]

Purpose: To develop a self‐supervised learning method to retrospectively estimate T1 and T2 values from clinical weighted MRI. Methods: A self‐supervised learning approach was constructed to estimate T1, T2, and proton density maps from conventional T1‐ and T2‐weighted images. MR physics models were employed to regenerate the weighted images from the network outputs, and the network was optimized based on loss calculated between the synthesized and input weighted images, alongside additional constraints based on prior information. The method was evaluated on healthy volunteer data, with conventional mapping as references. The reproducibility was examined on two 3.0T scanners. Performance in tumor characterization was inspected by applying the method to a public glioblastoma dataset. Results: For T1 and T2 estimation from three weighted images (T1 MPRAGE, T1 gradient echo sequences, and T2 turbo spin echo), the deep learning method achieved global voxel‐wise error ≤9% in brain parenchyma and regional error ≤12.2% in six types of brain tissues. The regional measurements obtained from two scanners showed mean differences ≤2.4% and correlation coefficients >0.98, demonstrating excellent reproducibility. In the 50 glioblastoma patients, the retrospective quantification results were in line with literature reports from prospective methods, and the T2 values were found to be higher in tumor regions, with sensitivity of 0.90 and specificity of 0.92 in a voxel‐wise classification task between normal and abnormal regions. Conclusion: The self‐supervised learning method is promising for retrospective T1 and T2 quantification from clinical MR images, with the potential to improve the availability of quantitative MRI and facilitate brain tumor characterization. [ABSTRACT FROM AUTHOR]

BackgroundLarge-vessel atherosclerotic disease is an important pathogenesis of deep-perforator infarction (DPI). However, altered vessel walls of intracranial large arteries and distribution of small arteries in DPI are unclear because of the limited resolution of current imaging techniques. In this study the intracranial plaque burden and lenticulostriate artery (LSA) distribution in patients with recent DPI and non-DPI using whole-brain vessel-wall imaging (WB-VWI) were investigated.MethodsA total of 44 patients with recent DPI (23 patients) or non-DPI (21 patients) due to intracranial atherosclerotic disease were prospectively enrolled. WB-VWI was performed in all the patients using a three-dimensional T1-weighted vessel-wall magnetic resonance technique. Hemispheres with DPI and non-DPI were considered as the DPI group and non-DPI group, respectively. Hemispheres without a history of stroke were the control group. The intracranial plaque burden was compared between the DPI and non-DPI groups. The number and length of visualized LSA branches among DPI, non-DPI, and control groups were also evaluated.ResultsA total of 77 hemispheres were analyzed (23 in the DPI group, 21 in the non-DPI group, and 33 in the control group). Plaque burden was lower (p = 0.047) in the DPI group (82.0 ± 45.9 mm3) compared with the non-DPI group (130.9 ± 90.3 mm3). There was a significant reduction (p = 0.002) in length of visualized LSA branches in the DPI group (74.1 ± 21.7 mm) compared with the control group (104.6 ± 33.3 mm).ConclusionsWB-VWI enables the combination of vessel-wall and LSA imaging in one image setting, which can provide information about plaque burden and LSA distribution.

BackgroundPancreatic ductal adenocarcinoma has dismal prognosis. Most patients receive radiation therapy (RT), which is complicated by respiration induced organ motion in upper abdomen. The purpose of this study is to report our early clinical experience in a novel self-gated k-space sorted four-dimensional magnetic resonance imaging (4D-MRI) with slab-selective (SS) excitation to highlight tumor infiltrating blood vessels for pancreatic RT.MethodsTen consecutive patients with borderline resectable or locally advanced pancreatic cancer were recruited to the study. Non-contrast 4D-MRI with and without slab-selective excitation and 4D-CT with delay contrast were performed on all patients. Vessel-tissue CNR were calculated for aorta and critical vessels (superior mesenteric artery or superior mesenteric vein) encompassed by tumor. Respiratory motion trajectories for tumor, as well as involved vessels were analyzed on SS-4D-MRI. Intra-class cross correlation (ICC) between tumor volume and involved vessels were calculated.ResultsAmong all 4D imaging modalities evaluated, SS-4D-MRI sampling trajectory results in images with highest vessel-tissue CNR comparing to non-slab-selective 4D-MRI and 4D-CT for all patients studied. Average (±standard deviation) CNR for involved vessels are 13.1 ± 8.4 and 3.2 ± 2.7 for SS-4D-MRI and 4D-CT, respectively. The ICC factors comparing tumor and involved vessels motion trajectories are 0.93 ± 0.10, 0.65 ± 0.31 and 0.77 ± 0.23 for superior-inferior, anterior-posterior and medial-lateral directions respectively.ConclusionsA novel 4D-MRI sequence based on 3D-radial sampling and slab-selective excitation has been assessed for pancreatic cancer patients. The non-contrast 4D-MRI images showed significantly better contrast to noise ratio for the vessels that limit tumor resectability compared to 4D-CT with delayed contrast. The sequence has great potential in accurately defining both the tumor and boost volume margins for pancreas RT with simultaneous integrated boost.

BackgroundCoronary high intensity plaques (CHIPs) detected using cardiovascular magnetic resonance (CMR) coronary atherosclerosis T1-weighted characterization with integrated anatomical reference (CATCH) have been shown to be positively associated with high-risk morphology observed on intracoronary optical coherence tomography (OCT). This study sought to validate whether CHIPs detected on CATCH indicate the presence of intraplaque hemorrhage (IPH) through ex vivo imaging of carotid and coronary plaque specimens, with histopathology as the standard reference.MethodsTen patients scheduled to undergo carotid endarterectomy underwent CMR with the conventional T1-weighted (T1w) sequence. Eleven carotid atherosclerotic plaques removed at carotid endarterectomy and six coronary artery endarterectomy specimens removed from patients undergoing coronary artery bypass grafting (CABG) were scanned ex vivo using both the conventional T1w sequence and CATCH. Both in vivo and ex vivo images were examined for the presence of IPH. The sensitivity, specificity, and Cohen Kappa (k) value of each scan were calculated using matched histological sections as the reference. k value between each scan in the discrimination of IPH was also computed.ResultsA total of 236 in vivo locations, 328 ex vivo and matching histology locations were included for the analysis. Sensitivity, specificity, and k value were 76.7%, 95.3%, and 0.75 for in vivo T1w imaging, 77.2%, 97.4%, and 0.78 for ex vivo T1w imaging, and 95.0%, 92.1%, and 0.84 for ex vivo CATCH, respectively. Moderate agreement was reached between in vivo T1w imaging, ex vivo T1w imaging, and ex vivo CATCH for the detection of IPH: between in vivo T1w imaging and ex vivo CATCH (k = 0.68), between ex vivo T1w imaging and ex vivo CATCH (k = 0.74), between in vivo T1w imaging and ex vivo T1w imaging (k = 0.83). None of the coronary artery plaque locations showed IPH.ConclusionThis study demonstrated that carotid CHIPs detected by CATCH can be used to assess for IPH, a high-risk plaque feature.

BACKGROUND:One of the potentially important applications of three-dimensional (3D) intracranial vessel wall (IVW) cardiovascular magnetic resonance (CMR) is to monitor disease progression and regression via quantitative measurement of IVW morphology during medical management or drug development. However, a prerequisite for this application is to validate that IVW morphologic measurements based on the modality are reliable. In this study we performed comprehensive reliability analysis for the recently proposed whole-brain IVW CMR technique. METHODS:Thirty-four healthy subjects and 10 patients with known intracranial atherosclerotic disease underwent repeat whole-brain IVW CMR scans. In 19 of the 34 subjects, two-dimensional (2D) turbo spin-echo (TSE) scan was performed to serve as a reference for the assessment of vessel dimensions. Lumen and wall volume, normalized wall index, mean and maximum wall thickness were measured in both 3D and 2D IVW CMR images. Scan-rescan, intra-observer, and inter-observer reproducibility of 3D IVW CMR in the quantification of IVW or plaque dimensions were respectively assessed in volunteers and patients as well as for different healthy subjectsub-groups (i.e.  0.75). In addition, all ICCs of patients were equal to or higher than that of healthy subjects except maximum wall thickness. In volunteers, all ICCs of the age group of ≥50 years were equal to or higher than that of the age group of

BackgroundIt has recently been shown that magnetic resonance (MR) "native T1" mapping is capable of characterizing abnormal microcirculation in patients with obstructive coronary artery disease (CAD). In studies involving women with signs and symptoms of ischemia and no obstructive CAD (INOCA), however, the potential role of native T1 as an imaging marker and its association with indices of diastolic function or vasodilator-induced myocardial ischemia have not been explored. We investigated whether native T1 in INOCA is associated with reduced myocardial perfusion reserve index (MPRI) or with diastolic dysfunction.MethodsTwenty-two female patients with INOCA and twelve female reference controls with matching age and body-mass index were studied. The patients had evidence of vasodilator-induced ischemia without obstructive CAD or any prior infarction. All 34 subjects underwent stress/rest MR including native T1 mapping (MOLLI 5(3)3) at 1.5-Tesla.ResultsCompared with controls, patients had similar morphology/function. As expected, MPRI was significantly reduced in patients compared to controls (1.78 ± 0.39 vs. 2.49 ± 0.41, p

PurposeThere is an increased interest to determine the exchange rate using CEST to provide pH information. However, current CEST quantification methods require lengthy scan times and do not address magnetization transfer effects. The purpose of this work was to apply the magnetic resonance fingerprinting (MRF) concept to CEST to achieve more efficient and accurate exchange rate quantification.MethodsThe proposed CEST fingerprinting method used varying saturation powers and saturation times to create unique signal evolutions for different exchange rates. The acquired signal was matched to a predefined dictionary to determine the exchange rate. The magnetization transfer effects were also addressed in the framework of CEST fingerprinting: The simulated dictionary could predict the signal curves without magnetization transfer effects, and comparing the dictionary to the acquired signals allowed the correction of the magnetization transfer effects. The CEST fingerprinting method was compared with the conventional pulsed quantitative CEST method using omega plots in the creatine phantom study.ResultsThe CEST fingerprinting method has a significantly reduced scan time (10 minutes versus 50 minutes) while providing more accurate exchange rate quantification using literature values as the reference.ConclusionIn this study, we demonstrate that CEST fingerprinting is more efficient (5 times faster) compared with pulsed quantitative CEST. It is also shown that the results of the proposed CEST fingerprinting technique are much closer to the literature values than pulsed quantitative CEST at 3 T.

Intracranial atherosclerotic disease tends to affect multiple arterial segments. Using whole-brain vessel wall imaging, we sought to study the differences in plaque features among various types of plaques in patients with a recent unilateral anterior circulation ischemic stroke. Sixty-one patients with unilateral anterior circulation ischemic stroke were referred to undergo whole-brain vessel wall imaging (before and after contrast) within 1 month of symptom onset for intracranial atherosclerotic disease evaluations. Each plaque was classified as a culprit, probably culprit, or nonculprit lesion, according to its likelihood of causing the stroke. The associations between plaque features (thickening pattern, plaque-wall contrast ratio, high signal on T1-weighted images, plaque contrast enhancement ratio, enhancement grade, and enhancement pattern) and culprit lesions were estimated using mixed multivariable logistic regression after adjustment for maximum wall thickness. In 52 patients without motion corruption in whole-brain vessel wall imaging, a total of 178 intracranial plaques in the anterior circulation were identified, including 52 culprit lesions (29.2%), 51 probably culprit lesions (28.7%), and 75 nonculprit lesions (42.1%). High signal on T1-weighted images (adjusted odds ratio, 9.1; 95% confidence interval, 1.9-44.1; P=0.006), grade 2 (enhancement ratio of plaque ≥ enhancement ratio of pituitary) contrast enhancement (adjusted odds ratio, 17.4; 95% confidence interval, 1.8-164.9; P=0.013), and type 2 (≥50% cross-sectional wall involvement) enhancement pattern (adjusted odds ratio, 10.1; 95% confidence interval, 1.3-82.2; P=0.030) were independently associated with culprit lesions. High signal on T1-weighted images, grade 2 contrast enhancement, and type 2 enhancement pattern are associated with cerebrovascular ischemic events, which may provide valuable insights into risk stratification.

Quantitative cardiovascular magnetic resonance (CMR) imaging can be used to characterize fibrosis, oedema, ischaemia, inflammation and other disease conditions. However, the need to reduce artefacts arising from body motion through a combination of electrocardiography (ECG) control, respiration control, and contrast-weighting selection makes CMR exams lengthy. Here, we show that physiological motions and other dynamic processes can be conceptualized as multiple time dimensions that can be resolved via low-rank tensor imaging, allowing for motion-resolved quantitative imaging with up to four time dimensions. This continuous-acquisition approach, which we name cardiovascular MR multitasking, captures - rather than avoids - motion, relaxation and other dynamics to efficiently perform quantitative CMR without the use of ECG triggering or breath holds. We demonstrate that CMR multitasking allows for T1 mapping, T1-T2 mapping and time-resolved T1 mapping of myocardial perfusion without ECG information and/or in free-breathing conditions. CMR multitasking may provide a foundation for the development of setup-free CMR imaging for the quantitative evaluation of cardiovascular health.

In the context of myocardial perfusion imaging (MPI) with cardiac magnetic resonance (CMR), there is ongoing debate on the merits of using technically complex acquisition methods to achieve whole-heart spatial coverage, rather than conventional 3-slice acquisition. An adequately powered comparative study is difficult to achieve given the requirement for two separate stress CMR studies in each patient. The aim of this work is to draw relevant conclusions from SPECT MPI by comparing whole-heart versus simulated 3-slice coverage in a large existing dataset. SPECT data from 651 patients with suspected coronary artery disease who underwent invasive angiography were analyzed. A computational approach was designed to model 3-slice MPI by retrospective subsampling of whole- heart data. For both whole-heart and 3-slice approaches, the diagnostic performance and the stress total perfusion deficit (TPD) score-a measure of ischemia extent/severity-were quantified and compared. Diagnostic accuracy for the 3-slice and whole-heart approaches were similar (area under the curve: 0.843 vs. 0.855, respectively; P = 0.07). The majority (54%) of cases missed by 3-slice imaging had primarily apical ischemia. Whole-heart and 3-slice TPD scores were strongly correlated (R2 = 0.93, P

The object of the study was to reveal the fiber microstructural response with diffusion tensor cardiac magnetic resonance after intramyocardial exosomes secreted by cardiosphere-derived cells (CDCEXO) in chronic porcine myocardial infarction. Porcine with myocardial infarction underwent intramyocardial delivery of human CDCEXO and placebo in a randomized placebo-controlled study. Four weeks after injection, viability improved in the CDCEXO group, whereas myocardial fiber architecture and cardiac function were preserved. In the placebo group, fiber architecture and cardiac function declined. Myocardial regeneration by CDCEXO is not tumor-like; instead, details of tissue architecture are faithfully preserved, which may foster physiological excitation and contraction.

BACKGROUND:Previous studies have linked cardiac dysfunction to loss of metabolites in the creatine kinase system. Chemical exchange saturation transfer (CEST) is a promising metabolic cardiovascular magnetic resonance (CMR) imaging technique and has been applied in the heart for creatine mapping. However, current limitations include: (a) long scan time, (b) residual cardiac and respiratory motion, and (c) B0 field variations induced by respiratory motion. An improved CEST CMR technique was developed to address these problems. METHODS:Animals with chronic myocardial infarction (N = 15) were scanned using the proposed CEST CMR technique and a late gadolinium enhancement (LGE)  sequence as reference. The major improvements of the CEST CMR technique are: (a) Images were acquired by single-shot FLASH, significantly increasing the scan efficiency. (b) All images were registered to reduce the residual motion. (c) The acquired Z-spectrum was analyzed using 3-pool-model Lorentzian-line fitting to generate CEST signal, reducing the impact of B0 field shifting due to respiratory motion. Feasibility of the technique was tested in a porcine model with chronic myocardial infarction. CEST signal was measured in the scar, border zone and remote myocardium. Initial studies were performed in one patient. RESULTS:In all animals, healthy remote myocardial CEST signal was elevated (0.16 ± 0.02) compared to infarct CEST signal (0.09 ± 0.02, P

BackgroundIschemia, in the absence of obstructive coronary artery disease, is prevalent in women, and associated with increased risk for major cardiovascular events. Coronary microvascular dysfunction is prevalent in these patients, and associated with impaired diastolic function. Despite our general understanding, however, optimal treatment of this cohort remains elusive.MethodsTo address this knowledge gap, we performed an open-label treatment trial to assess whether phosphodiesterase type 5 inhibition improves coronary microvascular perfusion and diastolic function in women with signs and symptoms of ischemia but no evidence of obstructive coronary artery disease. Left ventricular morphology and function, along with myocardial perfusion reserve index, were assessed by contrast-enhanced cardiac magnetic resonance imaging.ResultsA total of five women enrolled of which four completed the trial, while one was withdrawn by the investigators after developing dyspnea 1 week after treatment. Her symptoms resolved after cessation of the study medication. In contrast to our hypothesis, phosphodiesterase type 5 inhibition reduced the rate of circumferential strain in diastole in all four women who completed the trial (that is, diastolic dysfunction). This impairment could not be explained by changes in heart rate, contractility, blood pressure, or preload, and was not associated with a change in myocardial perfusion reserve index. Frequency of angina also tended to increase with treatment, with the greatest increase occurring in the patient with the greatest impairment in diastolic strain.ConclusionsTaken together, these data question the efficacy of phosphodiesterase type 5 inhibition to treat women with ischemic heart disease, and highlight the need for further investigation.

PurposeIn radiation treatment planning for thoracic and abdominal tumors, 4D-MRI has shown promise in respiratory motion characterization with improved soft-tissue contrast compared to clinical standard, 4D computed tomography (4D-CT). This study aimed to further improve vessel-tissue contrast and overall image quality in 3D radial sampling-based 4D-MRI using a slab-selective (SS) excitation approach.MethodsThe technique was implemented in a 3D radial sampling with self-gating-based k-space sorting sequence. The SS excitation approach was compared to a non-selective (NS) approach in six cancer patients and two healthy volunteers at 3T. Improvements in vessel-tissue contrast ratio (CR) and vessel signal-to-noise ratio (SNR) were analyzed in five of the eight subjects. Image quality was visually assessed in all subjects on a 4-point scale (0: poor; 3: excellent). Tumor (patients) and pancreas (healthy) motion trajectories were compared between the two imaging approaches.ResultsCompared with NS-4D-MRI, SS-4D-MRI significantly improved the overall vessel-tissue CR (2.60 ± 3.97 vs. 1.03 ± 1.44, P < 0.05), SNR (63.33 ± 38.45 vs. 35.74 ± 28.59, P < 0.05), and image quality score (2.6 ± 0.5 vs. 1.4 ± 0.5, P = 0.02). Motion trajectories from the two approaches exhibited strong correlation in the superior-inferior (0.96 ± 0.06), but weaker in the anterior-posterior (0.78 ± 0.24) and medial-lateral directions (0.46 ± 0.44).ConclusionsThe proposed 4D-MRI with slab-selectively excited 3D radial sampling allows for improved blood SNR, vessel-tissue CR, and image quality.

PurposeTo propose and evaluate a parameter tune-up solution to expedite a three-dimensional (3D) variable-flip-angle turbo spin-echo (TSE) sequence for whole-brain intracranial vessel wall (IVW) imaging.Materials and methodsElliptical k-space sampling and prolonged echo train length (ETL), were used to expedite a 3D variable-flip-angle TSE-based sequence. To compensate for the potential loss in vessel wall signal, optimal combination of prescribed T2 and ETL was experimentally investigated on 22 healthy volunteers at 3 Tesla. The optimized protocol (7-8 min) was then compared with a previous protocol (reference protocol, 11-12 min) in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel wall sharpness, and wall delineation quality on a 4-point scale (0:poor; 3:excellent) in 10 healthy volunteers. A pilot study of five patients was performed and lesion delineation score was used to demonstrate the diagnostic quality.ResultsA protocol with ETL = 52 and prescribed T2  = 170 ms was deemed an optimized one, which, compared with the reference protocol, provided significantly improved wall SNR (12.0 ± 1.3 versus 10.0 ± 1.1; P = 0.002), wall-lumen CNR (9.7 ± 1.2 versus 8.0 ± 0.9; P = 0.002), wall-CSF CNR (2.8 ± 1.0 versus 1.7 ± 1.0; P = 0.026), similar vessel wall sharpness at both inner (1.59 ± 0.18 versus 1.58 ± 0.14, P = 0.87) and outer (1.71 ± 0.25 versus 1.83 ± 0.30; P = 0.18) boundaries, and comparable vessel wall delineation score for individual segments (1.95-3; P > 0.06). In all patients, atherosclerotic plaques (10) or wall dissection (5) were identified with a delineation score of 3 or 2.ConclusionA parameter tune-up solution can accelerate 3D variable-flip-angle TSE acquisitions, particularly allowed for expedited whole-brain IVW imaging with preserved wall delineation quality.Level of evidence2. Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:751-757.

This study sought to develop an automated segmentation approach based on histogram analysis of raw axial images acquired by light-sheet fluorescent imaging (LSFI) to establish rapid reconstruction of the 3-D zebrafish cardiac architecture in response to doxorubicin-induced injury and repair. Input images underwent a 4-step automated image segmentation process consisting of stationary noise removal, histogram equalization, adaptive thresholding, and image fusion followed by 3-D reconstruction. We applied this method to 3-month old zebrafish injected intraperitoneally with doxorubicin followed by LSFI at 3, 30, and 60 days post-injection. We observed an initial decrease in myocardial and endocardial cavity volumes at day 3, followed by ventricular remodeling at day 30, and recovery at day 60 (P

ObjectivesThe aim of this work is the development of coronary atherosclerosis T1-weighted characterization with integrated anatomical reference (CATCH) technique and the validation by comparison with high-risk plaque features (HRPF) observed on intracoronary optical coherence tomography (OCT) and invasive coronary angiography.BackgroundT1-weighted cardiac magnetic resonance with or without contrast media has been used for characterizing coronary atherosclerosis showing promising prognostic value. Several limitations include: 1) coverage is limited to proximal coronary segments; 2) spatial resolution is low and often anisotropic; and 3) a separate magnetic resonance angiography acquisition is needed to localize lesions.MethodsCATCH acquired dark-blood T1-weighted images and bright-blood anatomical reference images in an interleaved fashion. Retrospective motion correction with 100% respiratory gating efficiency was achieved. Reference control subjects (n = 13) completed both pre- and post-contrast scans. Stable angina patients (n = 30) completed pre-contrast scans, among whom 26 eligible patients also completed post-contrast scans. After cardiac magnetic resonance, eligible patients (n = 22) underwent invasive coronary angiography and OCT for the interrogation of coronary atherosclerosis. OCT images were assessed and scored for HRPF (lipid-richness, macrophages, cholesterol crystals, and microvessels) by 2 experienced analysts blinded to magnetic resonance results.ResultsPer-subject analysis showed none of the 13 reference control subjects had coronary hyperintensive plaques (CHIP) in either pre-contrast or post-contrast CATCH. Five patients had CHIP on pre-contrast CATCH and 5 patients had CHIP on post-contrast CATCH. Patients with CHIP had greater lipid abnormality than those without. Per-segment analysis showed elevated pre- and post-contrast plaque to myocardium signal ratio in the lesions with HRPF versus those without. Positive correlation was observed between plaque to myocardium signal ratio and OCT HRPF scoring. CHIP on pre-contrast CATCH were associated with significantly higher stenosis level than non-CHIP on invasive coronary angiography.ConclusionsCATCH provided accelerated whole heart coronary plaque characterization with simultaneously acquired anatomical reference. CHIP detected by CATCH showed positive association with high-risk plaque features on invasive imaging studies.

Myocardial blood flow (MBF) is the critical determinant of cardiac function. However, its response to increases in partial pressure of arterial CO2 (PaCO2), particularly with respect to adenosine, is not well characterized because of challenges in blood gas control and limited availability of validated approaches to ascertain MBF in vivo. Methods: By prospectively and independently controlling PaCO2 and combining it with 13N-ammonia PET measurements, we investigated whether a physiologically tolerable hypercapnic stimulus (∼25 mm Hg increase in PaCO2) can increase MBF to that observed with adenosine in 3 groups of canines: without coronary stenosis, subjected to non-flow-limiting coronary stenosis, and after preadministration of caffeine. The extent of effect on MBF due to hypercapnia was compared with adenosine. Results: In the absence of stenosis, mean MBF under hypercapnia was 2.1 ± 0.9 mL/min/g and adenosine was 2.2 ± 1.1 mL/min/g; these were significantly higher than at rest (0.9 ± 0.5 mL/min/g, P < 0.05) and were not different from each other (P = 0.30). Under left-anterior descending coronary stenosis, MBF increased in response to hypercapnia and adenosine (P < 0.05, all territories), but the effect was significantly lower than in the left-anterior descending coronary territory (with hypercapnia and adenosine; both P < 0.05). Mean perfusion defect volumes measured with adenosine and hypercapnia were significantly correlated (R = 0.85) and were not different (P = 0.12). After preadministration of caffeine, a known inhibitor of adenosine, resting MBF decreased; and hypercapnia increased MBF but not adenosine (P < 0.05). Conclusion: Arterial blood CO2 tension when increased by 25 mm Hg can induce MBF to the same level as a standard dose of adenosine. Prospectively targeted arterial CO2 has the capability to evolve as an alternative to current pharmacologic vasodilators used for cardiac stress testing.

PurposeAlthough three-dimensional (3D) turbo spin echo (TSE) with variable flip angles has proven to be useful for intracranial vessel wall imaging, it is associated with inadequate suppression of cerebrospinal fluid (CSF) signals and limited spatial coverage at 3 Tesla (T). This work aimed to modify the sequence and develop a protocol to achieve whole-brain, CSF-attenuated T1 -weighted vessel wall imaging.MethodsNonselective excitation and a flip-down radiofrequency pulse module were incorporated into a commercial 3D TSE sequence. A protocol based on the sequence was designed to achieve T1 -weighted vessel wall imaging with whole-brain spatial coverage, enhanced CSF-signal suppression, and isotropic 0.5-mm resolution. Human volunteer and pilot patient studies were performed to qualitatively and quantitatively demonstrate the advantages of the sequence.ResultsCompared with the original sequence, the modified sequence significantly improved the T1 -weighted image contrast score (2.07 ± 0.19 versus 3.00 ± 0.00, P = 0.011), vessel wall-to-CSF contrast ratio (0.14 ± 0.16 versus 0.52 ± 0.30, P = 0.007) and contrast-to-noise ratio (1.69 ± 2.18 versus 4.26 ± 2.30, P = 0.022). Significant improvement in vessel wall outer boundary sharpness was observed in several major arterial segments.ConclusionsThe new 3D TSE sequence allows for high-quality T1 -weighted intracranial vessel wall imaging at 3 T. It may potentially aid in depicting small arteries and revealing T1 -mediated high-signal wall abnormalities. Magn Reson Med 77:1142-1150, 2017. © 2016 International Society for Magnetic Resonance in Medicine.