Self-gated, dynamic contrast-enhanced magnetic resonance imaging with compressed-sensing reconstruction for evaluating endothelial permeability in the aortic root of atherosclerotic mice.

High-risk atherosclerotic plaques are characterized by active inflammation and abundant leaky microvessels. We present a self-gated, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquisition with compressed sensing reconstruction and apply it to assess longitudinal changes in endothelial permeability in the aortic root of Apoe-/- atherosclerotic mice during natural disease progression. Twenty-four, 8-week-old, female Apoe-/- mice were divided into four groups (n = 6 each) and imaged with self-gated DCE-MRI at 4, 8, 12, and 16 weeks after high-fat diet initiation, and then euthanized for CD68 immunohistochemistry for macrophages. Eight additional mice were kept on a high-fat diet and imaged longitudinally at the same time points. Aortic-root pseudo-concentration curves were analyzed using a validated piecewise linear model. Contrast agent wash-in and washout slopes (b1 and b2 ) were measured as surrogates of aortic root endothelial permeability and compared with macrophage density by immunohistochemistry. b2 , indicating contrast agent washout, was significantly higher in mice kept on an high-fat diet for longer periods of time (p = 0.03). Group comparison revealed significant differences between mice on a high-fat diet for 4 versus 16 weeks (p = 0.03). Macrophage density also significantly increased with diet duration (p = 0.009). Spearman correlation between b2 from DCE-MRI and macrophage density indicated a weak relationship between the two parameters (r = 0.28, p = 0.20). Validated piecewise linear modeling of the DCE-MRI data showed that the aortic root contrast agent washout rate is significantly different during disease progression. Further development of this technique from a single-slice to a 3D acquisition may enable better investigation of the relationship between in vivo imaging of endothelial permeability and atherosclerotic plaques' genetic, molecular, and cellular makeup in this important model of disease.

Scan-rescan measurement repeatability of 18F-FDG PET/MR imaging of vascular inflammation.

Non-invasive positron emission tomography (PET) of vascular inflammation and atherosclerotic plaque by identifying increased uptake of 18F-fluordeoxyglucose (18F-FDG) is a powerful tool for monitoring disease activity, progression, and its response to therapy. 18F-FDG PET/computed tomography (PET/CT) of the aorta and carotid arteries has become widely used to assess changes in inflammation in clinical trials. However, the recent advent of hybrid PET/magnetic resonance (PET/MR) scanners has advantages for vascular imaging due to the reduction in radiation exposure and improved soft tissue contrast of MR compared to CT. Important for research and clinical use is an understanding of the scan-rescan repeatability of the PET measurement. While this has been studied for PET/CT, no data is currently available for vascular PET/MR imaging. In this study, we determined the scan-rescan measurement repeatability of 18F-FDG PET/MR in the aorta and carotid arteries was less than 5%, comparable to similar findings for 18F-FDG PET/CT.

A Medical Student Postpartum Telehealth Initiative During the COVID-19 Pandemic.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on our health systems and delivery of care and on the disruption of medical education. It has forced hospitals to move to a telehealth model for prenatal and postpartum visits and expedite discharges for postpartum patients in order to reduce exposure. We describe our medical school and hospital system initiative to employ medical student volunteers for postpartum telehealth calls during the peak of the COVID-19 pandemic in New York City. DESCRIPTION: Ten medical students conducted phone interviews with postpartum patients within 72 h of discharge at three hospitals in a large NYC health system, with faculty preceptors at each site who provided daily call assignments and oversight. Students called patients to screen for risk factors for postpartum complications, including preeclampsia and postpartum depression; provide additional contraception counseling; and address newborn care and health. One week and 2 week post-discharge calls were also made for COVID-19 positive patients for ongoing symptom monitoring and counseling. ASSESSMENT: We found numerous opportunities for intervention in postpartum health via telehealth, including addressing pharmacy-related needs, patient counseling, improving pain management, and identifying patients in need of emergent re-evaluation. CONCLUSION: As this pandemic continues to evolve, our model demonstrates the feasibility of telehealth and medical student involvement in postpartum care and its benefits to patients, medical student learning, and alleviation of burden on obstetric staff.

Ultra-high resolution, 3-dimensional magnetic resonance imaging of the atherosclerotic vessel wall at clinical 7T.

Accurate quantification and characterization of atherosclerotic plaques with MRI requires high spatial resolution acquisitions with excellent image quality. The intrinsically better signal-to-noise ratio (SNR) at high-field clinical 7T compared to the widely employed lower field strengths of 1.5 and 3T may yield significant improvements to vascular MRI. However, 7T atherosclerosis imaging also presents specific challenges, related to local transmit coils and B1 field inhomogeneities, which may overshadow these theoretical gains. We present the development and evaluation of 3D, black-blood, ultra-high resolution vascular MRI on clinical high-field 7T in comparison lower-field 3T. These protocols were applied for in vivo imaging of atherosclerotic rabbits, which are often used for development, testing, and validation of translatable cardiovascular MR protocols. Eight atherosclerotic New Zealand White rabbits were imaged on clinical 7T and 3T MRI scanners using 3D, isotropic, high (0.63 mm3) and ultra-high (0.43 mm3) spatial resolution, black-blood MR sequences with extensive spatial coverage. Following imaging, rabbits were sacrificed for validation using fluorescence imaging and histology. Image quality parameters such as SNR and contrast-to-noise ratio (CNR), as well as morphological and functional plaque measurements (plaque area and permeability) were evaluated at both field strengths. Using the same or comparable imaging parameters, SNR and CNR were in general higher at 7T compared to 3T, with a median (interquartiles) SNR gain of +40.3 (35.3-80.1)%, and a median CNR gain of +68.1 (38.5-95.2)%. Morphological and functional parameters, such as vessel wall area and permeability, were reliably acquired at 7T and correlated significantly with corresponding, widely validated 3T vessel wall MRI measurements. In conclusion, we successfully developed 3D, black-blood, ultra-high spatial resolution vessel wall MRI protocols on a 7T clinical scanner. 7T imaging was in general superior to 3T with respect to image quality, and comparable in terms of plaque area and permeability measurements.

A Preliminary 18F-FDG-PET/MRI Study Shows Increased Vascular Inflammation in Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Recent data suggest that patients with atopic dermatitis (AD) have increased systemic immune activation and cardiovascular risk. However, unlike psoriasis, evaluation of active vascular inflammation using state-of-the-art imaging is lacking in AD. OBJECTIVE: To assess aortic and carotid vascular inflammation using 18F-fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging (18F-FDG-PET/MRI) imaging in moderate-to-severe AD versus healthy individuals. METHODS: A total of 27 patients with moderate-to-severe AD and 12 healthy controls were imaged using 18F-FDG-PET/MRI. Target-to-background ratio (TBR) values were calculated in multiple segments of the aorta and carotid vessels. RESULTS: Patients with AD had elevated aortic max TBR (fold change [FCH] = 1.45, P = .057) versus healthy controls and significantly elevated mean TBR (FCH = 1.20; P < .05) in the right carotid (RC) arteries versus controls. When examining greatest focal inflammation (most diseased segment [MDS] TBR), patients with AD had higher aortic inflammation (FCH = 1.28; P = .052). AD clinical severity significantly correlated with C-reactive protein (ρ = 0.60, P < .01) and with RC mean TBR levels (ρ = 0.60, P = .04). Stratifying patients into moderate-to-severe and very severe AD showed greater RC mean TBR in patients with very severe AD versus controls (FCH = 1.31; P = .02) and versus patients with moderate/severe AD (FCH = 1.23, P = .05). Aortic inflammation was also significantly greater in patients with very severe AD versus controls (max TBR: FCH = 1.6, P = .04; MDS TBR: FCH = 1.73, P = .03). CONCLUSIONS: This preliminary study is the first that establishes greater vascular (aorta and carotid) inflammation in moderate-to-severe AD versus healthy controls. Furthermore, very severe AD showed higher inflammation than both moderate/severe patients and healthy controls. Future studies with larger patient cohorts and evaluation before and after treatment are needed to determine the extent to which vascular inflammation in AD is modifiable.

Segmentation of carotid arterial walls using neural networks.

BACKGROUND: Automated, accurate, objective, and quantitative medical image segmentation has remained a challenging goal in computer science since its inception. This study applies the technique of convolutional neural networks (CNNs) to the task of segmenting carotid arteries to aid in the assessment of pathology. AIM: To investigate CNN's utility as an ancillary tool for researchers who require accurate segmentation of carotid vessels. METHODS: An expert reader delineated vessel wall boundaries on 4422 axial T2-weighted magnetic resonance images of bilateral carotid arteries from 189 subjects with clinically evident atherosclerotic disease. A portion of this dataset was used to train two CNNs (one to segment the vessel lumen and the other to segment the vessel wall) with the remaining portion used to test the algorithm's efficacy by comparing CNN segmented images with those of an expert reader. RESULTS: Overall quantitative assessment between automated and manual segmentations was determined by computing the DICE coefficient for each pair of segmented images in the test dataset for each CNN applied. The average DICE coefficient for the test dataset (CNN segmentations compared to expert's segmentations) was 0.96 for the lumen and 0.87 for the vessel wall. Pearson correlation values and the intra-class correlation coefficient (ICC) were computed for the lumen (Pearson = 0.98, ICC = 0.98) and vessel wall (Pearson = 0.88, ICC = 0.86) segmentations. Bland-Altman plots of area measurements for the CNN and expert readers indicate good agreement with a mean bias of 1%-8%. CONCLUSION: Although the technique produces reasonable results that are on par with expert human assessments, our application requires human supervision and monitoring to ensure consistent results. We intend to deploy this algorithm as part of a software platform to lessen researchers' workload to more quickly obtain reliable results.

Reproducibility of thrombus volume quantification in multicenter computed tomography pulmonary angiography studies.

AIM: To evaluate reproducibility of pulmonary embolism (PE) clot volume quantification using computed tomography pulmonary angiogram (CTPA) in a multicenter setting. METHODS: This study was performed using anonymized data in conformance with HIPAA and IRB Regulations (March 2015-November 2016). Anonymized CTPA data was acquired from 23 scanners from 18 imaging centers using each site's standard PE protocol. Two independent analysts measured PE volumes using a semi-automated region-growing algorithm on an FDA-approved image analysis platform. Total thrombus volume (TTV) was calculated per patient as the primary endpoint. Secondary endpoints were individual thrombus volume (ITV), Qanadli score and modified Qanadli score per patient. Inter- and intra-observer reproducibility were assessed using intra-class correlation coefficient (ICC) and Bland-Altman analysis. RESULTS: Analyst 1 found 72 emboli in the 23 patients with a mean number of emboli of 3.13 per patient with a range of 0-11 emboli per patient. The clot volumes ranged from 0.0041 - 47.34 cm3 (mean +/- SD, 5.93 +/- 10.15cm3). On the second read, analyst 1 found the same number and distribution of emboli with a range of volumes for read 2 from 0.0041 - 45.52 cm3 (mean +/- SD, 5.42 +/- 9.53cm3). Analyst 2 found 73 emboli in the 23 patients with a mean number of emboli of 3.17 per patient with a range of 0-11 emboli per patient. The clot volumes ranged from 0.00459-46.29 cm3 (mean +/- SD, 5.91 +/- 10.06 cm3). Inter- and intra-observer variability measurements indicated excellent reproducibility of the semi-automated method for quantifying PE volume burden. ICC for all endpoints was greater than 0.95 for inter- and intra-observer analysis. Bland-Altman analysis indicated no significant biases. CONCLUSION: Semi-automated region growing algorithm for quantifying PE is reproducible using data from multiple scanners and is a suitable method for image analysis in multicenter clinical trials.

Effect of varying computed tomography acquisition and reconstruction parameters on semi-automated clot volume quantification.

AIM: To examine effects of computed tomography (CT) image acquisition/reconstruction parameters on clot volume quantification in vitro for research method validation purposes. METHODS: This study was performed in conformance with HIPAA and IRB Regulations (March 2015-November 2016). A ten blood clot phantom was designed and scanned on a dual-energy CT scanner (SOMATOM Force, Siemens Healthcare GmBH, Erlangen, Germany) with varying pitch, iterative reconstruction, energy level and slice thickness. A range of clot and tube sizes were used in an attempt to replicate in vivo emboli found within central and segmental branches of the pulmonary arteries in patients with pulmonary emboli. Clot volume was the measured parameter and was analyzed by a single image analyst using a semi-automated region growing algorithm implemented in the FDA-approved Siemens syngo.via image analysis platform. Mixed model analysis was performed on the data. RESULTS: On the acquisition side, the continuous factor of energy showed no statistically significant effect on absolute clot volume quantification (P = 0.9898). On the other hand, when considering the fixed factor of pitch, there were statistically significant differences in clot volume quantification (P < 0.0001). On the reconstruction side, with the continuous factor of reconstruction slice thickness no statistically significant effect on absolute clot volume quantification was demonstrated (P = 0.4500). Also on the reconstruction side, with the fixed factor of using iterative reconstructions there was also no statistically significant effect on absolute clot volume quantification (P = 0.3011). In addition, there was excellent R2 correlation between the scale-measured mass of the clots both with respect to the CT measured volumes and with respect to volumes measure by the water displacement method. CONCLUSION: Aside from varying pitch, changing CT acquisition parameters and using iterative reconstructions had no significant impact on clot volume quantification with a semi-automated region growing algorithm.

Combined PET/DCE-MRI in a Rabbit Model of Atherosclerosis: Integrated Quantification of Plaque Inflammation, Permeability, and Burden During Treatment With a Leukotriene A4 Hydrolase Inhibitor.

OBJECTIVES: The authors sought to develop combined positron emission tomography (PET) dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to quantify plaque inflammation, permeability, and burden to evaluate the efficacy of a leukotriene A4 hydrolase (LTA4H) inhibitor in a rabbit model of atherosclerosis. BACKGROUND: Multimodality PET/MRI allows combining the quantification of atherosclerotic plaque inflammation, neovascularization, permeability, and burden by combined 18F-fluorodeoxyglucose (18F-FDG) PET, DCE-MRI, and morphological MRI. The authors describe a novel, integrated PET-DCE/MRI protocol to noninvasively quantify these parameters in aortic plaques of a rabbit model of atherosclerosis. As proof-of-concept, the authors apply this protocol to assess the efficacy of the novel LTA4H inhibitor BI691751. METHODS: New Zealand White male rabbits (N = 49) were imaged with integrated PET-DCE/MRI after atherosclerosis induction and 1 and 3 months after randomization into 3 groups: 1) placebo; 2) high-dose BI691751; and 3) low-dose BI691751. All animals were euthanized at the end of the study. RESULTS: Among the several metrics that were quantified, only maximum standardized uptake value and target-to-background ratio by 18F-FDG PET showed a modest, but significant, reduction in plaque inflammation in rabbits treated with low-dose BI691751 (p = 0.03), whereas no difference was detected in the high-fat diet and in the high-dose BI691751 groups. No differences in vessel wall area by MRI and area under the curve by DCE-MRI were detected in any of the groups. No differences in neovessel and macrophage density were found at the end of study among groups. CONCLUSIONS: The authors present a comprehensive, integrated 18F-FDG PET and DCE-MRI imaging protocol to noninvasively quantify plaque inflammation, neovasculature, permeability, and burden in a rabbit model of atherosclerosis on a simultaneous PET/MRI scanner. A modest reduction was found in plaque inflammation by 18F-FDG PET in the group treated with a low dose of the LTA4H inhibitor BI691751.

Feasibility of imaging superficial palmar arch using micro-ultrasound, 7T and 3T magnetic resonance imaging.

AIM: To demonstrate feasibility of vessel wall imaging of the superficial palmar arch using high frequency micro-ultrasound, 7T and 3T magnetic resonance imaging (MRI). METHODS: Four subjects (ages 22-50 years) were scanned on a micro-ultrasound system with a 45-MHz transducer (Vevo 2100, VisualSonics). Subjects' hands were then imaged on a 3T clinical MR scanner (Siemens Biograph MMR) using an 8-channel special purpose phased array carotid coil. Lastly, subjects' hands were imaged on a 7T clinical MR scanner (Siemens Magnetom 7T Whole Body Scanner) using a custom built 8-channel transmit receive carotid coil. All three imaging modalities were subjectively analyzed for image quality and visualization of the vessel wall. RESULTS: Results of this very preliminary study indicated that vessel wall imaging of the superficial palmar arch was feasible with a whole body 7T and 3T MRI in comparison with micro-ultrasound. Subjective analysis of image quality (1-5 scale, 1: poorest, 5: best) from B mode, ultrasound, 3T SPACE MRI and 7T SPACE MRI indicated that the image quality obtained at 7T was superior to both 3T MRI and micro-ultrasound. The 3D SPACE sequence at both 7T and 3T MRI with isotropic voxels allowed for multi-planar reformatting of images and allowed for less operator dependent results as compared to high frequency micro-ultrasound imaging. Although quantitative analysis revealed that there was no significant difference between the three methods, the 7T Tesla trended to have better visibility of the vessel and its wall. CONCLUSION: Imaging of smaller arteries at the 7T is feasible for evaluating atherosclerosis burden and may be of clinical relevance in multiple diseases.