Semi-automated Segmentation and Quantification of Perivascular Spaces at 7 Tesla in COVID-19.

While COVID-19 is primarily considered a respiratory disease, it has been shown to affect the central nervous system. Mounting evidence shows that COVID-19 is associated with neurological complications as well as effects thought to be related to neuroinflammatory processes. Due to the novelty of COVID-19, there is a need to better understand the possible long-term effects it may have on patients, particularly linkage to neuroinflammatory processes. Perivascular spaces (PVS) are small fluid-filled spaces in the brain that appear on MRI scans near blood vessels and are believed to play a role in modulation of the immune response, leukocyte trafficking, and glymphatic drainage. Some studies have suggested that increased number or presence of PVS could be considered a marker of increased blood-brain barrier permeability or dysfunction and may be involved in or precede cascades leading to neuroinflammatory processes. Due to their size, PVS are better detected on MRI at ultrahigh magnetic field strengths such as 7 Tesla, with improved sensitivity and resolution to quantify both concentration and size. As such, the objective of this prospective study was to leverage a semi-automated detection tool to identify and quantify differences in perivascular spaces between a group of 10 COVID-19 patients and a similar subset of controls to determine whether PVS might be biomarkers of COVID-19-mediated neuroinflammation. Results demonstrate a detectable difference in neuroinflammatory measures in the patient group compared to controls. PVS count and white matter volume were significantly different in the patient group compared to controls, yet there was no significant association between PVS count and symptom measures. Our findings suggest that the PVS count may be a viable marker for neuroinflammation in COVID-19, and other diseases which may be linked to neuroinflammatory processes.

Temporospatial characterization of ventricular wall motion with real-time cardiac magnetic resonance imaging in health and disease.

Cardiac magnetic resonance imaging (MRI) has been largely dependent on retrospective cine for data acquisition. Real-time imaging, although inferior in image quality to retrospective cine, is more informative about motion dynamics. We herein developed a real-time cardiac MRI approach to temporospatial characterization of left ventricle (LV) and right ventricle (RV) wall motion. This approach provided two temporospatial indices, temporal periodicity and spatial coherence, for quantitative assessment of ventricular function. In a cardiac MRI study, we prospectively investigated temporospatial characterization in reference to standard volumetric measurements with retrospective cine. The temporospatial indices were found to be effective for evaluating the difference of ventricular performance between the healthy volunteers and the heart failure (HF) patients (LV temporal periodicity 0.24 ± 0.037 vs. 0.14 ± 0.021; RV temporal periodicity 0.18 ± 0.030 vs. 0.10 ± 0.014; LV spatial coherence 0.52 ± 0.039 vs. 0.38 ± 0.040; RV spatial coherence 0.50 ± 0.036 vs. 0.35 ± 0.035; all in arbitrary unit). The HF patients and healthy volunteers were well differentiated in the scatter plots of spatial coherence and temporal periodicity while they were mixed in those of end-systolic volume (ESV) and ejection fraction (EF) from volumetric measurements. This study demonstrated the potential of real-time cardiac MRI for intricate analysis of ventricular function beyond retrospective cine.

Real-time exercise stress cardiac MRI with Fourier-series reconstruction from golden-angle radial data.

Magnetic resonance imaging (MRI) can measure cardiac response to exercise stress for evaluating and managing heart patients in the practice of clinical cardiology. However, exercise stress cardiac MRI have been clinically limited by the ability of available MRI techniques to quantitatively measure fast and unstable cardiac dynamics during exercise. The presented work is to develop a new real-time MRI technique for improved quantitative performance of exercise stress cardiac MRI. This technique seeks to represent real-time cardiac images as a sparse Fourier-series along the time. With golden-angle radial acquisition, parallel imaging and compressed sensing can be integrated into a linear system of equations for resolving Fourier coefficients that are in turn used to generate real-time cardiac images from the Fourier-series representation. Fourier-series reconstruction from golden-angle radial data can effectively address data insufficiency due to MRI speed limitation, providing a real-time approach to exercise stress cardiac MRI. To demonstrate the feasibility, an exercise stress cardiac MRI experiment was run to investigate biventricular response to in-scanner biking exercise in a cohort of sixteen healthy volunteers. It was found that Fourier-series reconstruction from golden-angle radial data effectively detected exercise-induced increase in stroke volume and ejection fraction in a healthy heart. The presented work will improve the applications of exercise stress cardiac MRI in the practice of clinical cardiology.

Cardiac balanced steady-state free precession MRI at 0.35 T: a comparison study with 1.5 T.

BACKGROUND: While low-field MRI is disadvantaged by a reduced signal-to-noise ratio (SNR) compared to higher fields, it has a number of useful features such as decreased SAR and shorter T1, and has shown promise for diagnostic imaging. This study demonstrates the feasibility of cardiac balanced steady-state free precession (bSSFP) MRI at 0.35 T and compares cardiac bSSFP MRI images at 0.35 T with those at 1.5 T. METHODS: Cardiac images were acquired in 7 healthy volunteers using an ECG-gated bSSFP cine sequence on a 0.35 T superconducting MR system as well as a clinical 1.5 T system. Blood and myocardium SNR and contrast-to-noise ratio (CNR) were computed. Subjective image scoring was used to compare the image quality between 0.35 and 1.5 T. RESULTS: Cardiac images at 0.35 T were successfully acquired in all volunteers. While the 0.35 T images were noisier than those at 1.5 T, blood, myocardium and papillary muscles could be clearly delineated. At 0.35 T, bSSFP images were acquired at flip angles as high as 150°. Maximum CNR was achieved at 130°. Image quality scoring showed that while at lower flip angles, the 0.35 T images had poorer quality than the 1.5 T, but with flip angles of 110 and 130, the image quality at 0.35 T had scores similar to those at 1.5 T. CONCLUSIONS: This study demonstrates that cardiac bSSFP imaging is highly feasible at 0.35 T.

Real-time cardiac MRI with radial acquisition and k-space variant reduced-FOV reconstruction.

This work aims to demonstrate that radial acquisition with k-space variant reduced-FOV reconstruction can enable real-time cardiac MRI with an affordable computation cost. Due to non-uniform sampling, radial imaging requires k-space variant reconstruction for optimal performance. By converting radial parallel imaging reconstruction into the estimation of correlation functions with a previously-developed correlation imaging framework, Cartesian k-space may be reconstructed point-wisely based on parallel imaging relationship between every Cartesian datum and its neighboring radial samples. Furthermore, reduced-FOV correlation functions may be used to calculate a subset of Cartesian k-space data for image reconstruction within a small region of interest, making it possible to run real-time cardiac MRI with an affordable computation cost. In a stress cardiac test where the subject is imaged during biking with a heart rate of >100 bpm, this k-space variant reduced-FOV reconstruction is demonstrated in reference to several radial imaging techniques including gridding, GROG and SPIRiT. It is found that the k-space variant reconstruction outperforms gridding, GROG and SPIRiT in real-time imaging. The computation cost of reduced-FOV reconstruction is ~2 times higher than that of GROG. The presented work provides a practical solution to real-time cardiac MRI with radial acquisition and k-space variant reduced-FOV reconstruction in clinical settings.

Respiratory motion-resolved, self-gated 4D-MRI using Rotating Cartesian K-space (ROCK): Initial clinical experience on an MRI-guided radiotherapy system.

PURPOSE: To optimize and evaluate the respiratory motion-resolved, self-gated 4D-MRI using Rotating Cartesian K-space (ROCK-4D-MRI) method in a 0.35 T MRI-guided radiotherapy (MRgRT) system. METHODS AND MATERIALS: The study included seven patients with abdominal tumors treated on the MRgRT system. ROCK-4D-MRI and 2D-CINE, was performed immediately after one of the treatment fractions. Motion quantification based on 4D-MRI was compared with those based on 2D-CINE. The image quality of 4D-MRI was evaluated against 4D-CT. The gross tumor volumes (GTV) were defined based on individual respiratory phases of both 4D-MRI and 4D-CT and compared for their variability over the respiratory cycle. RESULT: The motion measurements based on 4D-MRI matched well with 2D-CINE, with differences of 1.04 ±â€¯0.52 mm in the superior-inferior and 0.54 ±â€¯0.21 mm in the anterior-posterior directions. The image quality scores of 4D-MRI were significantly higher than 4D-CT, with better tumor contrast (3.29 ±â€¯0.76 vs. 1.86 ±â€¯0.90) and less motion artifacts (3.57 ±â€¯0.53 vs. 2.29 ±â€¯0.95). The GTVs were more consistent in 4D-MRI than in 4D-CT, with significantly smaller GTV variability (9.31 ±â€¯4.58% vs. 34.27 ±â€¯23.33%). CONCLUSION: Our study demonstrated the clinical feasibility of using the ROCK-4D-MRI to acquire high quality, respiratory motion-resolved 4D-MRI in a low-field MRgRT system. The 4D-MRI image could provide accurate dynamic information for radiotherapy treatment planning.

Myocardial T1 mapping for patients with implanted cardiac devices using wideband inversion recovery spoiled gradient echo readout.

PURPOSE: To develop and validate a technique for myocardial T1 mapping in patients with implantable cardioverter defibrillators (ICDs). METHODS: A MOLLI-based pulse sequence, named Wideband-FLASH-MOLLI, was developed by incorporating a fast low angle shot (FLASH) readout and a wideband inversion pulse. The performance of Wideband-FLASH-MOLLI was evaluated using phantom studies and validated in eight healthy volunteers and ten patients with ICDs at 1.5 Tesla. Comparisons were made between Wideband-FLASH-MOLLI, FLASH-MOLLI, and bSSFP-MOLLI sequences. RESULTS: In phantom studies, the maximum T1 estimation errors using Wideband-FLASH-MOLLI with and without an ICD were less than 3% for T1 range from 212 to 1673 ms. In all healthy volunteers, there was no significant native myocardial T1 estimation difference using Wideband-FLASH-MOLLI before and after the external attachment of an ICD to the body coil (1178 ± 27 ms versus 1174 ± 33 ms; P = 0.41). Due to the presence of an ICD, the magnitude images acquired using bSSFP-MOLLI and FLASH-MOLLI showed severe artifacts within the myocardium. In contrast, no or negligible device-induced artifacts were noted within the myocardial regions of the healthy volunteers or the patients with ICDs when using Wideband-FLASH-MOLLI. CONCLUSION: This study demonstrates the feasibility of using Wideband-FLASH-MOLLI to mitigate image artifacts and to produce accurate myocardial T1 maps in patients with ICDs. Magn Reson Med 77:1495-1504, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Highly Accelerated SSFP Imaging with Controlled Aliasing in Parallel Imaging and integrated-SSFP (CAIPI-iSSFP).

PURPOSE: To develop a novel combination of controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) with integrated SSFP (CAIPI-iSSFP) for accelerated SSFP imaging without banding artifacts at 3T. MATERIALS AND METHODS: CAIPI-iSSFP was developed by adding a dephasing gradient to the balanced SSFP (bSSFP) pulse sequence with a gradient area that results in 2π dephasing across a single pixel. Extended phase graph (EPG) simulations were performed to show the signal behaviors of iSSFP, bSSFP, and RF-spoiled gradient echo (SPGR) sequences. In vivo experiments were performed for brain and abdominal imaging at 3T with simultaneous multi-slice (SMS) acceleration factors of 2, 3 and 4 with CAIPI-iSSFP and CAIPI-bSSFP. The image quality was evaluated by measuring the relative contrast-to-noise ratio (CNR) and by qualitatively assessing banding artifact removal in the brain. RESULTS: Banding artifacts were removed using CAIPI-iSSFP compared to CAIPI-bSSFP up to an SMS factor of 4 and 3 on brain and liver imaging, respectively. The relative CNRs between gray and white matter were on average 18% lower in CAIPI-iSSFP compared to that of CAIPI-bSSFP. CONCLUSION: This study demonstrated that CAIPI-iSSFP provides up to a factor of four acceleration, while minimizing the banding artifacts with up to a 20% decrease in the relative CNR.

Modified wideband three-dimensional late gadolinium enhancement MRI for patients with implantable cardiac devices.

PURPOSE: To study the effects of cardiac devices on three-dimensional (3D) late gadolinium enhancement (LGE) MRI and to develop a 3D LGE protocol for implantable cardioverter defibrillator (ICD) patients with reduced image artifacts. THEORY AND METHODS: The 3D LGE sequence was modified by implementing a wideband inversion pulse, which reduces hyperintensity artifacts, and by increasing bandwidth of the excitation pulse. The modified wideband 3D LGE sequence was tested in phantoms and evaluated in six volunteers and five patients with ICDs. RESULTS: Phantom and in vivo studies results demonstrated extended signal void and ripple artifacts in 3D LGE that were associated with ICDs. The reason for these artifacts was slab profile distortion and the subsequent aliasing in the slice-encoding direction. The modified wideband 3D LGE provided significantly reduced ripple artifacts than 3D LGE with wideband inversion only. Comparison of 3D and 2D LGE images demonstrated improved spatial resolution of the heart using 3D LGE. CONCLUSION: Increased bandwidth of the inversion and excitation pulses can significantly reduce image artifacts associated with ICDs. Our modified wideband 3D LGE protocol can be readily used for imaging patients with ICDs given appropriate safety guidelines are followed.

Device artifact reduction for magnetic resonance imaging of patients with implantable cardioverter-defibrillators and ventricular tachycardia: late gadolinium enhancement correlation with electroanatomic mapping.

BACKGROUND: Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) of ventricular scar has been shown to be accurate for detection and characterization of arrhythmia substrates. However, the majority of patients referred for ventricular tachycardia (VT) ablation have an implantable cardioverter-defibrillator (ICD), which obscures image integrity and the clinical utility of MRI. OBJECTIVE: The purpose of this study was to develop and validate a wideband LGE MRI technique for device artifact removal. METHODS: A novel wideband LGE MRI technique was developed to allow for improved scar evaluation on patients with ICDs. The wideband technique and the standard LGE MRI were tested on 18 patients with ICDs. VT ablation was performed in 13 of 18 patients with either endocardial and/or epicardial approach and the correlation between the scar identified on MRI and electroanatomic mapping (EAM) was analyzed. RESULTS: Hyperintensity artifact was present in 16 of 18 of patients using standard MRI, which was eliminated using the wideband LGE and allowed for MRI interpretation in 15 of 16 patients. All patients had ICD lead characteristics confirmed as unchanged post-MRI and had no adverse events. LGE scar was seen in 11 of 18 patients. Among the 15 patients in whom wideband LGE allowed visualization of myocardium, 10 had LGE scar and 5 had normal myocardium in the regions with image artifacts when using the standard LGE. The left ventricular scar size measurements using wideband MRI and EAM were correlated with R(2) = 0.83 and P = .00003. CONCLUSION: Wideband LGE MRI improves the ability to visualize myocardium for clinical interpretation, which correlated well with EAM findings during VT ablation.

Improved late gadolinium enhancement MR imaging for patients with implanted cardiac devices.

PURPOSE: To propose and test a modified wideband late gadolinium enhancement (LGE) magnetic resonance (MR) imaging technique to overcome hyperintensity image artifacts caused by implanted cardiac devices. MATERIALS AND METHODS: Written informed consent was obtained from all participants, and the HIPAA-compliant study protocol was approved by the institutional review board. Studies in phantoms and in a healthy volunteer were performed to test the hypothesis that the hyperintensity artifacts that are typically observed on LGE images in patients with implanted cardiac devices are caused by insufficient inversion of the affected myocardial signal. The conventional LGE MR imaging pulse sequence was modified by replacing the nonselective inversion pulse with a wideband inversion pulse. The modified LGE sequence, along with the conventional LGE sequence, was evaluated in 12 patients with implantable cardioverter defibrillators (ICDs) who were referred for cardiac MR imaging. RESULTS: The ICD causes 2-6 kHz in frequency shift at locations 5-10 cm away from the device. This off-resonance falls outside the typical spectral bandwidth of the nonselective inversion pulse used in conventional LGE, which results in the hyperintensity artifact. In 10 of the 12 patients, the conventional LGE technique produced severe, uninterpretable hyperintensity artifacts in the anterior and lateral portions of the left ventricular wall. These artifacts were eliminated with use of the wideband LGE sequence, thereby enabling confident evaluation of myocardial viability. CONCLUSION: The modified wideband LGE MR imaging technique eliminates the hyperintensity artifacts seen in patients with cardiac devices. The technique may enable LGE MR imaging in patients with cardiac devices, in whom LGE MR imaging otherwise could not be used for diagnosis.

Neocortical capillary flow pulsatility is not elevated in experimental communicating hydrocephalus.

While communicating hydrocephalus (CH) is often characterized by increased pulsatile flow of cerebrospinal fluid (CSF) in the cerebral aqueduct, a clear-cut explanation for this phenomenon is lacking. Increased pulsatility of the entire cerebral vasculature including the cortical capillaries has been suggested as a causative mechanism. To test this theory, we used two-photon microscopy to measure flow pulsatility in neocortical capillaries 40 to 500 µm below the pial surface in adult rats with CH at 5 to 7 days (acute, n=8) and 3 to 5 weeks (chronic, n=5) after induction compared with intact controls (n=9). Averaging over all cortical depths, no increase in capillary pulsatility occurred in acute (pulsatility index (PI): 0.15±0.06) or chronic (0.14±0.05) CH animals compared with controls (0.18±0.07; P=0.07). More specifically, PI increased significantly with cortical depth in controls (r=0.35, P<0.001), but no such increase occurred in acute (r=0.06, P=0.3) or chronic (r=0.05, P=0.5) CH. Pulsatile CSF aqueductal flow, in contrast, was elevated 10- to 500-fold compared with controls. We conclude that even in the presence of markedly elevated pulsatile CSF flow in the aqueduct, there is no concurrent increase in microvascular pulsatile flow.

Elevated CSF outflow resistance associated with impaired lymphatic CSF absorption in a rat model of kaolin-induced communicating hydrocephalus.

BACKGROUND: We recently reported a lymphatic cerebrospinal fluid (CSF) absorption deficit in a kaolin model of communicating hydrocephalus in rats with ventricular expansion correlating negatively with the magnitude of the impediment to lymphatic function. However, it is possible that CSF drainage was not significantly altered if absorption at other sites compensated for the lymphatic defect. The purpose of this study was to investigate the impact of the lymphatic absorption deficit on global CSF absorption (CSF outflow resistance). METHODS: Kaolin was injected into the basal cisterns of Sprague Dawley rats. The development of hydrocephalus was assessed using magnetic resonance imaging (MRI). In one group of animals at about 3 weeks after injection, the movement of intraventricularly injected iodinated human serum albumin (125I-HSA) into the olfactory turbinates provided an estimate of CSF transport through the cribriform plate into nasal lymphatics (n = 18). Control animals received saline in place of kaolin (n = 10). In a second group at about 3.5 weeks after kaolin injection, intraventricular pressure was measured continuously during infusion of saline into the spinal subarachnoid space at various flow rates (n = 9). CSF outflow resistance was calculated as the slope of the steady-state pressure versus flow rate. Control animals for this group either received no injections (intact: n = 11) or received saline in place of kaolin (n = 8). RESULTS: Compared to saline injected controls, lateral ventricular volume in the kaolin group was significantly greater (0.087 +/- 0.013 ml, n = 27 versus 0.015 +/- 0.001 ml, n = 17) and lymphatic function was significantly less (2.14 +/- 0.72% injected/g, n = 18 versus 6.38 +/- 0.60% injected/g, n = 10). Additionally, the CSF outflow resistance was significantly greater in the kaolin group (0.46 +/- 0.04 cm H2O microL(-1) min, n = 9) than in saline injected (0.28 +/- 0.03 cm H2O microL(-1) min, n = 8) or intact animals (0.18 +/- 0.03 cm H2O microL(-1) min, n = 11). There was a significant positive correlation between CSF outflow resistance and ventricular volume. CONCLUSIONS: The data suggest that the impediment to lymphatic CSF absorption in a kaolin-induced model of communicating hydrocephalus has a significant impact on global CSF absorption. A lymphatic CSF absorption deficit would appear to play some role (either direct or indirect) in the pathogenesis of ventriculomegaly.