We investigated the ability of targeted immunomicelles to detect and assess macrophages in atherosclerotic plaque using MRI in vivo. There is a large clinical need for a noninvasive tool to assess ...atherosclerosis from a molecular and cellular standpoint. Macrophages play a central role in atherosclerosis and are associated with plaques vulnerable to rupture. Therefore, macrophage scavenger receptor (MSR) was chosen as a target for molecular MRI. MSR-targeted immunomicelles, micelles, and gadolinium-diethyltriaminepentaacetic acid (DTPA) were tested in ApoE-/- and WT mice by using in vivo MRI. Confocal laser-scanning microscopy colocalization, macrophage immunostaining and MRI correlation, competitive inhibition, and various other analyses were performed. In vivo MRI revealed that at 24 h postinjection, immunomicelles provided a 79% increase in signal intensity of atherosclerotic aortas in ApoE-/- mice compared with only 34% using untargeted micelles and no enhancement using gadolinium-DTPA. Confocal laser-scanning microscopy revealed colocalization between fluorescent immunomicelles and macrophages in plaques. There was a strong correlation between macrophage content in atherosclerotic plaques and the matched in vivo MRI results as measured by the percent normalized enhancement ratio. Monoclonal antibodies to MSR were able to significantly hinder immunomicelles from providing contrast enhancement of atherosclerotic vessels in vivo. Immunomicelles provided excellent validated in vivo enhancement of atherosclerotic plaques. The enhancement seen is related to the macrophage content of the atherosclerotic vessel areas imaged. Immunomicelles may aid in the detection of high macrophage content associated with plaques vulnerable to rupture.
To evaluate the capability of P947, a magnetic resonance (MR) imaging contrast agent that molecularly targets matrix metalloproteinases (MMPs), to aid detection and imaging of MMPs in atherosclerotic ...lesions in vivo; its specificity compared with that of P1135; expression and distribution of MMPs in atherosclerotic vessels; and in vivo distribution and molecular localization of fluorescent europium (Eu) P947.
The Animal Care and Use Committee approved all experiments. P947 was synthesized by attaching a gadolinium chelate (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) to a peptide that specifically binds MMPs. Scrambled form of P947 (P1135) was synthesized by replacing the targeting moiety of P947 with a scrambled peptide lacking the ability to bind MMPs. P947, P1135, and gadoterate meglumine were injected into atherosclerotic apolipoprotein E-deficient and wild-type mice. The aortic MR imaging enhancement produced by the contrast agents was measured at different times and was compared by using one-way analysis of variance. MMP expression was investigated in the aortas by using MMP immunostaining and in situ MMP zymography. A fluorescent form of P947 (Eu-P947) was synthesized to compare the in vivo distribution of the contrast agent (Eu-P947) with specific MMP immunofluorescent staining.
MMP-targeted P947 facilitated a 93% increase (P < .001) in MR image signal intensity (contrast-to-noise ratio CNR, 17.7 compared with 7.7; P < .001) of atherosclerotic lesions in vivo. Nontargeted P1135 (scrambled P947) provided 33% MR image enhancement (CNR, 10.8), whereas gadoterate meglumine provided 5% (CNR, 6.9). Confocal laser scanning microscopy demonstrated colocalization between fluorescent Eu-P947 and MMPs in atherosclerotic plaques. Eu-P947 was particularly present in the fibrous cap region of plaques.
P947 improved MR imaging for atherosclerosis through MMP-specific targeting. The results were validated and provide support for further assessment of P947 as a potential tool for the identification of unstable atherosclerosis.
Magnetic resonance imaging (MRI) has become integral to diagnosing and managing patients with suspected or confirmed prostate cancer. However, the benefits of utilizing MRI can be hindered by quality ...issues during imaging acquisition, interpretation, and reporting. As the utilization of prostate MRI continues to increase in clinical practice, the variability in MRI quality and how it can negatively impact patient care have become apparent. The American College of Radiology (ACR) has recognized this challenge and developed several initiatives to address the issue of inconsistent MRI quality and ensure that imaging centers deliver high-quality patient care. These initiatives include the Prostate Imaging Reporting and Data System (PI-RADS), developed in collaboration with an international panel of experts and members of the European Society of Urogenital Radiology (ESUR), the Prostate MR Image Quality Improvement Collaborative, which is part of the ACR Learning Network, the ACR Prostate Cancer MRI Center Designation, and the ACR Appropriateness Criteria. In this article, we will discuss the importance of these initiatives in establishing quality assurance and quality control programs for prostate MRI and how they can improve patient outcomes.
Variability in prostate MRI quality is an increasingly recognized problem that negatively affects patient care. This report aims to describe the results and key learnings of the first cohort of the ...ACR Learning Network Prostate MR Image Quality Improvement Collaborative.
Teams from five organizations in the United States were trained on a structured improvement method. After reaching a consensus on image quality and auditing their images using the Prostate Imaging Quality (PI-QUAL) system, teams conducted a current state analysis to identify barriers to obtaining high-quality images. Through plan-do-study-act cycles involving frontline staff, each site designed and tested interventions targeting image quality key drivers. The percentage of examinations meeting quality criteria (ie, PI-QUAL score ≥4) was plotted on a run chart, and project progress was reviewed in weekly meetings. At the collaborative level, the goal was to increase the percentage of examinations with PI-QUAL ≥4 to at least 85%.
Across 2,380 examinations audited, the mean weekly rates of prostate MR examinations meeting image quality criteria increased from 67% (range: 60%-74%) at baseline to 87% (range: 80%-97%) upon program completion. The most commonly employed interventions were MR protocol adjustments, development and implementation of patient preparation instructions, personnel training, and development of an auditing process mechanism.
A learning network model, in which organizations share knowledge and work together toward a common goal, can improve prostate MR image quality at multiple sites simultaneously. The inaugural cohort’s key learnings provide a road map for improvement on a broader scale.
Purpose To study the effect of extraocular muscle surgery on intraocular pressure (IOP) in patients with thyroid-associated ophthalmopathy. Design Retrospective, observational case series. Methods ...The medical records of patients with restrictive myopathy secondary to thyroid-associated ophthalmopathy who underwent strabismus surgery from July 1, 1997 through July 31, 2003 were reviewed and analyzed retrospectively. Seventeen patients met the criteria and were included in this study. All patients were seen at the Thyroid Eye Center at the University of California, San Diego, a university-based tertiary referral center. The main outcome measure was IOP readings obtained before and after surgery in both primary gaze and upgaze. Results A statistically significant decrease in IOP in upgaze was noted after extraocular muscle recession. The mean IOP before surgery was 16.6 ± 3.78 mm Hg in primary gaze and 23.2 ± 7.27 mm Hg in upgaze. After strabismus surgery, the mean IOP after one month was 15.7 ± 2.36 mm Hg ( P = .215) in primary gaze and 18.9 ± 2.96 mm Hg in upgaze ( P = .001). Conclusions Strabismus surgery resulted in a significant reduction in IOP in the early postoperative period in patients with restrictive myopathy secondary to thyroid-associated ophthalmopathy.
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