Automated intracranial vessel segmentation of 4D flow MRI data in patients with atherosclerotic stenosis using a convolutional neural network.

Introduction: Intracranial 4D flow MRI enables quantitative assessment of hemodynamics in patients with intracranial atherosclerotic disease (ICAD). However, quantitative assessments are still challenging due to the time-consuming vessel segmentation, especially in the presence of stenoses, which can often result in user variability. To improve the reproducibility and robustness as well as to accelerate data analysis, we developed an accurate, fully automated segmentation for stenosed intracranial vessels using deep learning. Methods: 154 dual-VENC 4D flow MRI scans (68 ICAD patients with stenosis, 86 healthy controls) were retrospectively selected. Manual segmentations were used as ground truth for training. For automated segmentation, deep learning was performed using a 3D U-Net. 20 randomly selected cases (10 controls, 10 patients) were separated and solely used for testing. Cross-sectional areas and flow parameters were determined in the Circle of Willis (CoW) and the sinuses. Furthermore, the flow conservation error was calculated. For statistical comparisons, Dice scores (DS), Hausdorff distance (HD), average symmetrical surface distance (ASSD), Bland-Altman analyses, and interclass correlations were computed using the manual segmentations from two independent observers as reference. Finally, three stenosis cases were analyzed in more detail by comparing the 4D flow-based segmentations with segmentations from black blood vessel wall imaging (VWI). Results: Training of the network took approximately 10 h and the average automated segmentation time was 2.2 ± 1.0 s. No significant differences in segmentation performance relative to two independent observers were observed. For the controls, mean DS was 0.85 ± 0.03 for the CoW and 0.86 ± 0.06 for the sinuses. Mean HD was 7.2 ± 1.5 mm (CoW) and 6.6 ± 3.7 mm (sinuses). Mean ASSD was 0.15 ± 0.04 mm (CoW) and 0.22 ± 0.17 mm (sinuses). For the patients, the mean DS was 0.85 ± 0.04 (CoW) and 0.82 ± 0.07 (sinuses), the HD was 8.4 ± 3.1 mm (CoW) and 5.7 ± 1.9 mm (sinuses) and the mean ASSD was 0.22 ± 0.10 mm (CoW) and 0.22 ± 0.11 mm (sinuses). Small bias and limits of agreement were observed in both cohorts for the flow parameters. The assessment of the cross-sectional lumen areas in stenosed vessels revealed very good agreement (ICC: 0.93) with the VWI segmentation but a consistent overestimation (bias ± LOA: 28.1 ± 13.9%). Discussion: Deep learning was successfully applied for fully automated segmentation of stenosed intracranial vasculatures using 4D flow MRI data. The statistical analysis of segmentation and flow metrics demonstrated very good agreement between the CNN and manual segmentation and good performance in stenosed vessels. To further improve the performance and generalization, more ICAD segmentations as well as other intracranial vascular pathologies will be considered in the future.

lGeneralized super-resolution 4D Flow MRI-using ensemble learning to extend across the cardiovascular system.

4D Flow Magnetic Resonance Imaging (4D Flow MRI) is a non-invasive measurement technique capable of quantifying blood flow across the cardiovascular system. While practical use is limited by spatial resolution and image noise, incorporation of trained super-resolution (SR) networks has potential to enhance image quality post-scan. However, these efforts have predominantly been restricted to narrowly defined cardiovascular domains, with limited exploration of how SR performance extends across the cardiovascular system; a task aggravated by contrasting hemodynamic conditions apparent across the cardiovasculature. The aim of our study was to explore the generalizability of SR 4D Flow MRI using a combination of heterogeneous training sets and dedicated ensemble learning. With synthetic training data generated across three disparate domains (cardiac, aortic, cerebrovascular), varying convolutional base and ensemble learners were evaluated as a function of domain and architecture, quantifying performance on both in-silico and acquired in-vivo data from the same three domains. Results show that both bagging and stacking ensembling enhance SR performance across domains, accurately predicting high-resolution velocities from low-resolution input data in-silico. Likewise, optimized networks successfully recover native resolution velocities from downsampled in-vivo data, as well as show qualitative potential in generating denoised SR-images from clinicallevel input data. In conclusion, our work presents a viable approach for generalized SR 4D Flow MRI, with ensemble learning extending utility across various clinical areas of interest.

Fast myocardial T1ρ mapping in mice using k-space weighted image contrast and a Bloch simulation-optimized radial sampling pattern.

PURPOSE: T1ρ dispersion quantification can potentially be used as a cardiac magnetic resonance index for sensitive detection of myocardial fibrosis without the need of contrast agents. However, dispersion quantification is still a major challenge, because T1ρ mapping for different spin lock amplitudes is a very time consuming process. This study aims to develop a fast and accurate T1ρ mapping sequence, which paves the way to cardiac T1ρ dispersion quantification within the limited measurement time of an in vivo study in small animals. METHODS: A radial spin lock sequence was developed using a Bloch simulation-optimized sampling pattern and a view-sharing method for image reconstruction. For validation, phantom measurements with a conventional sampling pattern and a gold standard sequence were compared to examine T1ρ quantification accuracy. The in vivo validation of T1ρ mapping was performed in N = 10 mice and in a reproduction study in a single animal, in which ten maps were acquired in direct succession. Finally, the feasibility of myocardial dispersion quantification was tested in one animal. RESULTS: The Bloch simulation-based sampling shows considerably higher image quality as well as improved T1ρ quantification accuracy (+ 56%) and precision (+ 49%) compared to conventional sampling. Compared to the gold standard sequence, a mean deviation of - 0.46 ± 1.84% was observed. The in vivo measurements proved high reproducibility of myocardial T1ρ mapping. The mean T1ρ in the left ventricle was 39.5 ± 1.2 ms for different animals and the maximum deviation was 2.1% in the successive measurements. The myocardial T1ρ dispersion slope, which was measured for the first time in one animal, could be determined to be 4.76 ± 0.23 ms/kHz. CONCLUSION: This new and fast T1ρ quantification technique enables high-resolution myocardial T1ρ mapping and even dispersion quantification within the limited time of an in vivo study and could, therefore, be a reliable tool for improved tissue characterization.

2D Projection Maps of WSS and OSI Reveal Distinct Spatiotemporal Changes in Hemodynamics in the Murine Aorta during Ageing and Atherosclerosis.

Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient (Apoe-/-, n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe-/- mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability.

Evaluation of Plaque Characteristics and Inflammation Using Magnetic Resonance Imaging.

Atherosclerosis is an inflammatory disease of large and medium-sized arteries, characterized by the growth of atherosclerotic lesions (plaques). These plaques often develop at inner curvatures of arteries, branchpoints, and bifurcations, where the endothelial wall shear stress is low and oscillatory. In conjunction with other processes such as lipid deposition, biomechanical factors lead to local vascular inflammation and plaque growth. There is also evidence that low and oscillatory shear stress contribute to arterial remodeling, entailing a loss in arterial elasticity and, therefore, an increased pulse-wave velocity. Although altered shear stress profiles, elasticity and inflammation are closely intertwined and critical for plaque growth, preclinical and clinical investigations for atherosclerosis mostly focus on the investigation of one of these parameters only due to the experimental limitations. However, cardiovascular magnetic resonance imaging (MRI) has been demonstrated to be a potent tool which can be used to provide insights into a large range of biological parameters in one experimental session. It enables the evaluation of the dynamic process of atherosclerotic lesion formation without the need for harmful radiation. Flow-sensitive MRI provides the assessment of hemodynamic parameters such as wall shear stress and pulse wave velocity which may replace invasive and radiation-based techniques for imaging of the vascular function and the characterization of early plaque development. In combination with inflammation imaging, the analyses and correlations of these parameters could not only significantly advance basic preclinical investigations of atherosclerotic lesion formation and progression, but also the diagnostic clinical evaluation for early identification of high-risk plaques, which are prone to rupture. In this review, we summarize the key applications of magnetic resonance imaging for the evaluation of plaque characteristics through flow sensitive and morphological measurements. The simultaneous measurements of functional and structural parameters will further preclinical research on atherosclerosis and has the potential to fundamentally improve the detection of inflammation and vulnerable plaques in patients.

Simultaneous measurements of 3D wall shear stress and pulse wave velocity in the murine aortic arch.

PURPOSE: Wall shear stress (WSS) and pulse wave velocity (PWV) are important parameters to characterize blood flow in the vessel wall. Their quantification with flow-sensitive phase-contrast (PC) cardiovascular magnetic resonance (CMR), however, is time-consuming. Furthermore, the measurement of WSS requires high spatial resolution, whereas high temporal resolution is necessary for PWV measurements. For these reasons, PWV and WSS are challenging to measure in one CMR session, making it difficult to directly compare these parameters. By using a retrospective approach with a flexible reconstruction framework, we here aimed to simultaneously assess both PWV and WSS in the murine aortic arch from the same 4D flow measurement. METHODS: Flow was measured in the aortic arch of 18-week-old wildtype (n = 5) and ApoE-/- mice (n = 5) with a self-navigated radial 4D-PC-CMR sequence. Retrospective data analysis was used to reconstruct the same dataset either at low spatial and high temporal resolution (PWV analysis) or high spatial and low temporal resolution (WSS analysis). To assess WSS, the aortic lumen was labeled by semi-automatically segmenting the reconstruction with high spatial resolution. WSS was determined from the spatial velocity gradients at the lumen surface. For calculation of the PWV, segmentation data was interpolated along the temporal dimension. Subsequently, PWV was quantified from the through-plane flow data using the multiple-points transit-time method. Reconstructions with varying frame rates and spatial resolutions were performed to investigate the influence of spatiotemporal resolution on the PWV and WSS quantification. RESULTS: 4D flow measurements were conducted in an acquisition time of only 35 min. Increased peak flow and peak WSS values and lower errors in PWV estimation were observed in the reconstructions with high temporal resolution. Aortic PWV was significantly increased in ApoE-/- mice compared to the control group (1.7 ± 0.2 versus 2.6 ± 0.2 m/s, p < 0.001). Mean WSS magnitude values averaged over the aortic arch were (1.17 ± 0.07) N/m2 in wildtype mice and (1.27 ± 0.10) N/m2 in ApoE-/- mice. CONCLUSION: The post processing algorithm using the flexible reconstruction framework developed in this study permitted quantification of global PWV and 3D-WSS in a single acquisition. The possibility to assess both parameters in only 35 min will markedly improve the analyses and information content of in vivo measurements.

Fast self-navigated wall shear stress measurements in the murine aortic arch using radial 4D-phase contrast cardiovascular magnetic resonance at 17.6 T.

PURPOSE: 4D flow cardiovascular magnetic resonance (CMR) and the assessment of wall shear stress (WSS) are non-invasive tools to study cardiovascular risks in vivo. Major limitations of conventional triggered methods are the long measurement times needed for high-resolution data sets and the necessity of stable electrocardiographic (ECG) triggering. In this work an ECG-free retrospectively synchronized method is presented that enables accelerated high-resolution measurements of 4D flow and WSS in the aortic arch of mice. METHODS: 4D flow and WSS were measured in the aortic arch of 12-week-old wildtype C57BL/6 J mice (n = 7) with a radial 4D-phase-contrast (PC)-CMR sequence, which was validated in a flow phantom. Cardiac and respiratory motion signals were extracted from the radial CMR signal and were used for the reconstruction of 4D-flow data. Rigid motion correction and a first order B0 correction was used to improve the robustness of magnitude and velocity data. The aortic lumen was segmented semi-automatically. Temporally averaged and time-resolved WSS and oscillatory shear index (OSI) were calculated from the spatial velocity gradients at the lumen surface at 14 locations along the aortic arch. Reproducibility was tested in 3 animals and the influence of subsampling was investigated. RESULTS: Volume flow, cross-sectional areas, WSS and the OSI were determined in a measurement time of only 32 min. Longitudinal and circumferential WSS and radial stress were assessed at 14 analysis planes along the aortic arch. The average longitudinal, circumferential and radial stress values were 1.52 ± 0.29 N/m2, 0.28 ± 0.24 N/m2 and - 0.21 ± 0.19 N/m2, respectively. Good reproducibility of WSS values was observed. CONCLUSION: This work presents a robust measurement of 4D flow and WSS in mice without the need of ECG trigger signals. The retrospective approach provides fast flow quantification within 35 min and a flexible reconstruction framework.

Assessment of local pulse wave velocity distribution in mice using k-t BLAST PC-CMR with semi-automatic area segmentation.

BACKGROUND: Local aortic pulse wave velocity (PWV) is a measure for vascular stiffness and has a predictive value for cardiovascular events. Ultra high field CMR scanners allow the quantification of local PWV in mice, however these systems are yet unable to monitor the distribution of local elasticities. METHODS: In the present study we provide a new accelerated method to quantify local aortic PWV in mice with phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) at 17.6 T. Based on a k-t BLAST (Broad-use Linear Acquisition Speed-up Technique) undersampling scheme, total measurement time could be reduced by a factor of 6. The fast data acquisition enables to quantify the local PWV at several locations along the aortic blood vessel based on the evaluation of local temporal changes in blood flow and vessel cross sectional area. To speed up post processing and to eliminate operator bias, we introduce a new semi-automatic segmentation algorithm to quantify cross-sectional areas of the aortic vessel. The new methods were applied in 10 eight-month-old mice (4 C57BL/6J-mice and 6 ApoE (-/-)-mice) at 12 adjacent locations along the abdominal aorta. RESULTS: Accelerated data acquisition and semi-automatic post-processing delivered reliable measures for the local PWV, similiar to those obtained with full data sampling and manual segmentation. No statistically significant differences of the mean values could be detected for the different measurement approaches. Mean PWV values were elevated for the ApoE (-/-)-group compared to the C57BL/6J-group (3.5 ± 0.7 m/s vs. 2.2 ± 0.4 m/s, p < 0.01). A more heterogeneous PWV-distribution in the ApoE (-/-)-animals could be observed compared to the C57BL/6J-mice, representing the local character of lesion development in atherosclerosis. CONCLUSION: In the present work, we showed that k-t BLAST PC-MRI enables the measurement of the local PWV distribution in the mouse aorta. The semi-automatic segmentation method based on PC-CMR data allowed rapid determination of local PWV. The findings of this study demonstrate the ability of the proposed methods to non-invasively quantify the spatial variations in local PWV along the aorta of ApoE (-/-)-mice as a relevant model of atherosclerosis.

MRI-based quantification of renal perfusion in mice: Improving sensitivity and stability in FAIR ASL.

PURPOSE: The importance of the orientation of the selective inversion slice in relation to the anatomy in flow-sensitive alternating inversion recovery arterial spin labeling (FAIR ASL) kidney perfusion measurements is demonstrated by comparing the standard FAIR scheme to a scheme with an improved slice selective control experiment. METHODS: A FAIR ASL method is used. The selective inversion preparation slice is set perpendicular to the measurement slice to decrease the unintended labeling of arterial spins in the control experiment. A T1*-based quantification method compensates for the effects of the imperfect inversion on the edge of the selective inversion slice. The quantified perfusion values are compared to the standard experiment with parallel orientation of imaging and selective inversion slice. RESULTS: Perfusion maps acquired with the perpendicular inversion slice orientation show higher sensitivity compared to the parallel orientation. The T1*-based quantification method removes artifacts arising from imperfect inversion slice profiles. The stability is improved. CONCLUSION: Adjusting the labeling technique to the anatomy is of high importance. Improved sensitivity and reproducibility could be demonstrated. The proposed method provides a solution to the problem of FAIR ASL measurements of renal perfusion in coronal view.

Local versus global aortic pulse wave velocity in early atherosclerosis: An animal study in ApoE-/--mice using ultrahigh field MRI.

Increased aortic stiffness is known to be associated with atherosclerosis and has a predictive value for cardiovascular events. This study aims to investigate the local distribution of early arterial stiffening due to initial atherosclerotic lesions. Therefore, global and local pulse wave velocity (PWV) were measured in ApoE-/- and wild type (WT) mice using ultrahigh field MRI. For quantification of global aortic stiffness, a new multi-point transit-time (TT) method was implemented and validated to determine the global PWV in the murine aorta. Local aortic stiffness was measured by assessing the local PWV in the upper abdominal aorta, using the flow/area (QA) method. Significant differences between age matched ApoE-/- and WT mice were determined for global and local PWV measurements (global PWV: ApoE-/-: 2.7±0.2m/s vs WT: 2.1±0.2m/s, P<0.03; local PWV: ApoE-/-: 2.9±0.2m/s vs WT: 2.2±0.2m/s, P<0.03). Within the WT mouse group, the global PWV correlated well with the local PWV in the upper abdominal aorta (R2 = 0.75, P<0.01), implying a widely uniform arterial elasticity. In ApoE-/- animals, however, no significant correlation between individual local and global PWV was present (R2 = 0.07, P = 0.53), implying a heterogeneous distribution of vascular stiffening in early atherosclerosis. The assessment of global PWV using the new multi-point TT measurement technique was validated against a pressure wire measurement in a vessel phantom and showed excellent agreement. The experimental results demonstrate that vascular stiffening caused by early atherosclerosis is unequally distributed over the length of large vessels. This finding implies that assessing heterogeneity of arterial stiffness by multiple local measurements of PWV might be more sensitive than global PWV to identify early atherosclerotic lesions.

Self-navigation under non-steady-state conditions: Cardiac and respiratory self-gating of inversion recovery snapshot FLASH acquisitions in mice.

PURPOSE: An algorithm is presented to enable cardiac and respiratory self-gating in combination with Inversion Recovery Look-Locker read-outs. METHODS: A radial inversion recovery snapshot FLASH sequence was adapted for retrospective cardiac T1 measurements in mice. Cardiac and respiratory data were extracted from the k-space center of radial projections and an adapted method for retrospective cardiac synchronization is introduced. Electrocardiogram (ECG) data was acquired concurrently for validation of the proposed self-gating technique. T1 maps generated by the proposed technique were compared with maps reconstructed with the ECG reference. RESULTS: Respiratory gating and cardiac trigger points could be obtained for the whole time course of the relaxation dynamic and correlate very well to the ECG signal. T1 maps reconstructed with the self-gating technique are in very good agreement with maps reconstructed with the external reference. CONCLUSION: The proposed method extends "wireless" cardiac MRI to non-steady-state inversion recovery measurements. T1 maps were generated with a quality comparable to ECG based reconstructions. As the method does not rely on an ECG trigger signal it provides easier animal handling. Magn Reson Med 76:1887-1894, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Initial investigation of a novel noninvasive weight loss therapy using MRI-Guided high intensity focused ultrasound (MR-HIFU) of visceral fat.

PURPOSE: MRI-guided high intensity focused ultrasound (MR-HIFU) allows noninvasive heating of deep tissues. Specifically targeting visceral fat deposits with MR-HIFU could offer an effective therapy for reversing the development of obesity, diabetes, and metabolic syndrome. METHODS: Overweight rats received either MR-HIFU of visceral fat, sham treatment, no treatment, or ex vivo temperature calibration. Conventional MR thermometry methods are not effective in fat tissue. Therefore, the T2 of fat was used to estimate heating in adipose tissue. RESULTS: HIFU treated rats lost 7.5% of their body weight 10 days after HIFU, compared with 1.9% weight loss in sham animals (P = 0.008) and 1.3% weight increase in untreated animals (P = 0.004). Additionally, the abdominal fat volume in treated animals decreased by 8.2 mL 7 days after treatment (P = 0.002). The T2 of fat at 1.5 Tesla increased by 3.3 ms per °C. The fat T2 was 103.3 ms before HIFU, but increased to 128.7 ms (P = 0.0005) after HIFU at 70 watts for 16 s and to 131.9 ms (P = 0.0005) after HIFU at 100 watts for 16 s. CONCLUSION: These experiments demonstrate that MR-HIFU of visceral fat could provide a safe, effective, and noninvasive weight loss therapy for combating obesity and the subsequent medical complications. Magn Reson Med 76:282-289, 2016. © 2015 Wiley Periodicals, Inc.

Quantification of perfusion in murine myocardium: A retrospectively triggered T1 -based ASL method using model-based reconstruction.

PURPOSE: A method for the quantification of perfusion in murine myocardium is demonstrated. The method allows for the reconstruction of perfusion maps on arbitrary time points in the heart cycle while addressing problems that arise due to the irregular heart beat of mice. METHODS: A flow-sensitive alternating inversion recovery arterial spin labeling method using an untriggered FLASH-read out with random sampling is used. Look-Locker conditions are strictly maintained. No dummy pulses or mechanism to reduce deviation from Look-Locker conditions are needed. Electrocardiogram and respiratory data are recorded for retrospective gating and triggering. A model-based technique is used to reconstruct missing k-space data to cope with the undersampling inherent in retrospectively gated methods. Acquisition and reconstruction were validated numerically and in phantom measurements before in vivo experimentation. RESULTS: Quantitative perfusion maps were acquired within a single slice measurement time of 11 min. Perfusion values are in good accordance to literature values. Myocardial infarction could be clearly visualized and results were confirmed with histological results. CONCLUSION: The proposed method is capable of producing quantitative perfusion maps on arbitrary positions in the heart cycle within a short measurement time. The method is robust against irregular breathing patterns and heart rate changes and can be implemented on all scanners.

Imaging of brain tumors with paramagnetic vesicles targeted to phosphatidylserine.

PURPOSE: To investigate paramagnetic saposin C and dioleylphosphatidylserine (SapC-DOPS) vesicles as a targeted contrast agent for imaging phosphatidylserine (PS) expressed by glioblastoma multiforme (GBM) tumors. MATERIALS AND METHODS: Gd-DTPA-BSA/SapC-DOPS vesicles were formulated, and the vesicle diameter and relaxivity were measured. Targeting of Gd-DTPA-BSA/SapC-DOPS vesicles to tumor cells in vitro and in vivo was compared with nontargeted paramagnetic vesicles (lacking SapC). Mice with GBM brain tumors were imaged at 3, 10, 20, and 24 h postinjection to measure the relaxation rate (R1) in the tumor and the normal brain. RESULTS: The mean diameter of vesicles was 175 nm, and the relaxivity at 7 Tesla was 3.32 (s*mM)(-1) relative to the gadolinium concentration. Gd-DTPA-BSA/SapC-DOPS vesicles targeted cultured cancer cells, leading to an increased R1 and gadolinium level in the cells. In vivo, Gd-DTPA-BSA/SapC-DOPS vesicles produced a 9% increase in the R1 of GBM brain tumors in mice 10 h postinjection, but only minimal changes (1.2% increase) in the normal brain. Nontargeted paramagnetic vesicles yielded minimal change in the tumor R1 at 10 h postinjection (1.3%). CONCLUSION: These experiments demonstrate that Gd-DTPA-BSA/SapC-DOPS vesicles can selectively target implanted brain tumors in vivo, providing noninvasive mapping of the cancer biomarker PS.

Perfluorocarbon nanoparticles: evolution of a multimodality and multifunctional imaging agent.

Perfluorocarbon nanoparticles offer a biologically inert, highly stable, and nontoxic platform that can be specifically designed to accomplish a range of molecular imaging and drug delivery functions in vivo. The particle surface can be decorated with targeting ligands to direct the agent to a variety of biomarkers that are associated with diseases such as cancer, cardiovascular disease, obesity, and thrombosis. The surface can also carry a high payload of imaging agents, ranging from paramagnetic metals for MRI, radionuclides for nuclear imaging, iodine for CT, and florescent tags for histology, allowing high sensitivity mapping of cellular receptors that may be expressed at very low levels in the body. In addition to these diagnostic imaging applications, the particles can be engineered to carry highly potent drugs and specifically deposit them into cell populations that display biosignatures of a variety of diseases. The highly flexible and robust nature of this combined molecular imaging and drug delivery vehicle has been exploited in a variety of animal models to demonstrate its potential impact on the care and treatment of patients suffering from some of the most debilitating diseases.

Myocardial perfusion quantification using the T1 -based FAIR-ASL method: the influence of heart anatomy, cardiopulmonary blood flow and look-locker readout.

PURPOSE: The quantification of myocardial perfusion using a Look-Locker flow-sensitive alternating inversion recovery- arterial spin labeling experiment is considered. Due to the anatomy of the heart, a substantial but unintended partial inversion of the inflowing blood occurs during the slice-selective inversion. Both, the partial inversion as well as the Look-Locker pulse train, influence the myocardial perfusion quantification and are addressed in this work. METHODS: The mean relaxation time approximation is used to calculate the monoexponential relaxation time of the signal in perfused tissue under Look-Locker readout. The left ventricular blood serves as an approximation of the inflowing blood in the description of FAIR-ASL measurements with global and slice-selective inversion to correctly quantify the myocardial perfusion. RESULTS: The analysis shows that the myocardial perfusion can be overestimated if the T1 -based quantification method is not adapted respecting the Look-Locker pulse train explicitly. Additionally, it turns out that without correction for the partial inversion of the blood pool during the slice-selective inversion the myocardial perfusion is underestimated. CONCLUSION: It is shown that the Look-Locker readout as well as the nonideal slice-selective inversion experiment have a considerable influence and have to be included properly to correctly quantify myocardial perfusion.

Fast retrospectively triggered local pulse-wave velocity measurements in mice with CMR-microscopy using a radial trajectory.

BACKGROUND: The aortic pulse-wave velocity (PWV) is an important indicator of cardiovascular risk. In recent studies MRI methods have been developed to measure this parameter noninvasively in mice. Present techniques require additional hardware for cardiac and respiratory gating. In this work a robust self-gated measurement of the local PWV in mice without the need of triggering probes is proposed. METHODS: The local PWV of 6-months-old wild-type C57BL/6J mice (n=6) was measured in the abdominal aorta with a retrospectively triggered radial Phase Contrast (PC) MR sequence using the flow-area (QA) method. A navigator signal was extracted from the CMR data of highly asymmetric radial projections with short repetition time (TR=3 ms) and post-processed with high-pass and low-pass filters for retrospective cardiac and respiratory gating. The self-gating signal was used for a reconstruction of high-resolution Cine frames of the aortic motion. To assess the local PWV the volume flow Q and the cross-sectional area A of the aorta were determined. The results were compared with the values measured with a triggered Cartesian and an undersampled triggered radial PC-Cine sequence. RESULTS: In all examined animals a self-gating signal could be extracted and used for retrospective breath-gating and PC-Cine reconstruction. With the non-triggered measurement PWV values of 2.3±0.2 m/s were determined. These values are in agreement with those measured with the triggered Cartesian (2.4±0.2 m/s) and the triggered radial (2.3±0.2 m/s) measurement. Due to the strong robustness of the radial trajectory against undersampling an acceleration of more than two relative to the prospectively triggered Cartesian sampling could be achieved with the retrospective method. CONCLUSION: With the radial flow-encoding sequence the extraction of a self-gating signal is feasible. The retrospective method enables a robust and fast measurement of the local PWV without the need of additional trigger hardware.

Molecular MR imaging of neovascular progression in the Vx2 tumor with αvß3-targeted paramagnetic nanoparticles.

PURPOSE: To assess the dependence of neovascular molecular magnetic resonance (MR) imaging on relaxivity (r1) of αvß3-targeted paramagnetic perfluorocarbon (PFC) nanoparticles and to delineate the temporal-spatial consistency of angiogenesis assessments for individual animals. MATERIALS AND METHODS: Animal protocols were approved by the Washington University Animal Studies Committee. Proton longitudinal and transverse relaxation rates of αvß3-targeted and nontargeted PFC nanoparticles incorporating gadolinium diethylenetrianime pentaacedic acid (Gd-DTPA) bisoleate (BOA) or gadolinium tetraazacyclododecane tetraacetic acid (Gd-DOTA) phosphatidylethanolamine (PE) into the surfactant were measured at 3.0 T. These paramagnetic nanoparticles were compared in 30 New Zealand White rabbits (four to six rabbits per group) 14 days after implantation of a Vx2 tumor. Subsequently, serial MR (3.0 T) neovascular maps were developed 8, 14, and 16 days after tumor implantation by using αvß3-targeted Gd-DOTA-PE nanoparticles (n = 4) or nontargeted Gd-DOTA-PE nanoparticles (n = 4). Data were analyzed with analysis of variance and nonparametric statistics. RESULTS: At 3.0 T, Gd-DTPA-BOA nanoparticles had an ionic r1 of 10.3 L · mmol(-1) · sec(-1) and a particulate r1 of 927000 L · mmol(-1) · sec(-1). Gd-DOTA-PE nanoparticles had an ionic r1 of 13.3 L · mmol(-1) · sec(-1) and a particulate r1 of 1 197000 L · mmol(-1) · sec(-1). Neovascular contrast enhancement in Vx2 tumors (at 14 days) was 5.4% ± 1.06 of the surface volume with αvß3-targeted Gd-DOTA-PE nanoparticles and 3.0% ± 0.3 with αvß3-targeted Gd-DTPA-BOA nanoparticles (P = .03). MR neovascular contrast maps of tumors 8, 14, and 16 days after implantation revealed temporally consistent and progressive surface enhancement (1.0% ± 0.3, 4.5% ± 0.9, and 9.3% ± 1.4, respectively; P = .0008), with similar time-dependent changes observed among individual animals. CONCLUSION: Temporal-spatial patterns of angiogenesis for individual animals were followed to monitor longitudinal tumor progression. Neovasculature enhancement was dependent on the relaxivity of the targeted agent.

An MRI system for imaging neonates in the NICU: initial feasibility study.

BACKGROUND: Transporting premature infants from a neonatal intensive care unit (NICU) to a radiology department for MRI has medical risks and logistical challenges. OBJECTIVE: To develop a small 1.5-T MRI system for neonatal imaging that can be easily installed in the NICU and to evaluate its performance using a sheep model of human prematurity. MATERIALS AND METHODS: A 1.5-T MRI system designed for orthopedic use was adapted for neonatal imaging. The system was used for MRI examinations of the brain, chest and abdomen in 12 premature lambs during the first hours of life. Spin-echo, fast spin-echo and gradient-echo MR images were evaluated by two pediatric radiologists. RESULTS: All animals remained physiologically stable throughout the imaging sessions. Animals were imaged at two or three time points. Seven brain MRI examinations were performed in seven different animals, 23 chest examinations in 12 animals and 19 abdominal examinations in 11 animals. At each anatomical location, high-quality images demonstrating good spatial resolution, signal-to-noise ratio and tissue contrast were routinely obtained within 30 min using standard clinical protocols. CONCLUSION: Our preliminary experience demonstrates the feasibility and potential of the neonatal MRI system to provide state-of-the-art MRI capabilities within the NICU. Advantages include overall reduced cost and site demands, lower acoustic noise, improved ease of access and reduced medical risk to the neonate.