Philip M. Robson

Atherosclerotic plaque targeting mechanism of long-circulating nanoparticles established by multimodal imaging.

Atherosclerosis is a major cause of global morbidity and mortality that could benefit from novel targeted therapeutics. Recent studies have shown efficient and local drug delivery with nanoparticles, although the nanoparticle targeting mechanism for atherosclerosis has not yet been fully elucidated. Here we used in vivo and ex vivo multimodal imaging to examine permeability of the vessel wall and atherosclerotic plaque accumulation of fluorescently labeled liposomal nanoparticles in a rabbit model. We found a strong correlation between permeability as established by in vivo dynamic contrast enhanced magnetic resonance imaging and nanoparticle plaque accumulation with subsequent nanoparticle distribution throughout the vessel wall. These key observations will enable the development of nanotherapeutic strategies for atherosclerosis.

DCE-MRI of the liver: effect of linear and nonlinear conversions on hepatic perfusion quantification and reproducibility.

To evaluate the effect of different methods to convert magnetic resonance (MR) signal intensity (SI) to gadolinium concentration ([Gd]) on estimation and reproducibility of model‐free and modeled hepatic perfusion parameters measured with dynamic contrast‐enhanced (DCE)‐MRI.

Gadolinium-Based Contrast Agents for Vessel Wall Magnetic Resonance Imaging (MRI) of Atherosclerosis

Cardiovascular disease due to atherosclerosis is the number one killer in the Western world, and threatens to become the major cause of morbidity and mortality worldwide. It is therefore paramount to develop non-invasive methods for the detection of high-risk, asymptomatic individuals before the onset of clinical symptoms or events. In the recent past, great strides have been made in the understanding of the pathological mechanisms involved in the atherosclerotic cascade down to the molecular details. This has allowed the development of contrast agents that can aid in the in vivo characterization of these processes. Gadolinium chelates are among the contrast media most commonly used in MR imaging. Originally used for MR angiography for the detection and quantification of vascular stenosis, more recently they have been applied to improve characterization of atherosclerotic plaques. In this manuscript, we will briefly review gadolinium-chelates (Gd) based contrast agents for non-invasive MR imaging of atherosclerosis. We will first describe Gd-based non-targeted FDA approved agents, used routinely in clinical practice for the evaluation of neovascularization in other diseases. Secondly, we will describe non-specific and specific targeted contrast agents, which have great potential for dissecting specific biological processes in the atherosclerotic cascade. Lastly, we will briefly compare Gd-based agents to others commonly used in MRI and to other imaging modalities.

Three-dimensional dynamic contrast-enhanced MRI for the accurate, extensive quantification of microvascular permeability in atherosclerotic plaques.

Atherosclerotic plaques that cause stroke and myocardial infarction are characterized by increased microvascular permeability and inflammation. Dynamic contrast‐enhanced MRI (DCE‐MRI) has been proposed as a method to quantify vessel wall microvascular permeability in vivo. Until now, most DCE‐MRI studies of atherosclerosis have been limited to two‐dimensional (2D) multi‐slice imaging. Although providing the high spatial resolution required to image the arterial vessel wall, these approaches do not allow the quantification of plaque permeability with extensive anatomical coverage, an essential feature when imaging heterogeneous diseases, such as atherosclerosis. To our knowledge, we present the first systematic evaluation of three‐dimensional (3D), high‐resolution, DCE‐MRI for the extensive quantification of plaque permeability along an entire vascular bed, with validation in atherosclerotic rabbits. We compare two acquisitions: 3D turbo field echo (TFE) with motion‐sensitized‐driven equilibrium (MSDE) preparation and 3D turbo spin echo (TSE). We find 3D TFE DCE‐MRI to be superior to 3D TSE DCE‐MRI in terms of temporal stability metrics. Both sequences show good intra‐ and inter‐observer reliability, and significant correlation with ex vivo permeability measurements by Evans Blue near‐infrared fluorescence (NIRF). In addition, we explore the feasibility of using compressed sensing to accelerate 3D DCE‐MRI of atherosclerosis, to improve its temporal resolution and therefore the accuracy of permeability quantification. Using retrospective under‐sampling and reconstructions, we show that compressed sensing alone may allow the acceleration of 3D DCE‐MRI by up to four‐fold. We anticipate that the development of high‐spatial‐resolution 3D DCE‐MRI with prospective compressed sensing acceleration may allow for the more accurate and extensive quantification of atherosclerotic plaque permeability along an entire vascular bed. We foresee that this approach may allow for the comprehensive and accurate evaluation of plaque permeability in patients, and may be a useful tool to assess the therapeutic response to approved and novel drugs for cardiovascular disease. Copyright

Attenuation correction for flexible magnetic resonance coils in combined magnetic resonance/positron emission tomography imaging.

IntroductionAttenuation correction for magnetic resonance (MR) coils is a new challenge that came about with the development of combined MR and positron emission tomography (PET) imaging. This task is difficult because such coils are not directly visible on either PET or MR acquisitions with current combined scanners and are therefore not easily localized in the field of view. This issue becomes more evident when trying to localize flexible MR coils (eg, cardiac or body matrix coil) that change position and shape from patient to patient and from one imaging session to another. In this study, we proposed a novel method to localize and correct for the attenuation and scatter of a flexible MR cardiac coil, using MR fiducial markers placed on the surface of the coil to allow for accurate registration of a template computed tomography (CT)–based attenuation map. Materials and MethodsTo quantify the attenuation properties of the cardiac coil, a uniform cylindrical water phantom injected with 18F-fluorodeoxyglucose (18F-FDG) was imaged on a sequential MR/PET system with and without the flexible cardiac coil. After establishing the need to correct for the attenuation of the coil, we tested the feasibility of several methods to register a precomputed attenuation map to correct for the attenuation. To accomplish this, MR and CT visible markers were placed on the surface of the cardiac flexible coil. Using only the markers as a driver for registration, the CT image was registered to the reference image through a combination of rigid and deformable registration. The accuracy of several methods was compared for the deformable registration, including B-spline, thin-plate spline, elastic body spline, and volume spline. Finally, we validated our novel approach both in phantom and patient studies. ResultsThe findings from the phantom experiments indicated that the presence of the coil resulted in a 10% reduction in measured 18F-FDG activity when compared with the phantom-only scan. Local underestimation reached 22% in regions of interest close to the coil. Various registration methods were tested, and the volume spline was deemed to be the most accurate, as measured by the Dice similarity metric. The results of our phantom experiments showed that the bias in the 18F-FDG quantification introduced by the presence of the coil could be reduced by using our registration method. An overestimation of only 1.9% of the overall activity for the phantom scan with the coil attenuation map was measured when compared with the baseline phantom scan without coil. A local overestimation of less than 3% was observed in the ROI analysis when using the proposed method to correct for the attenuation of the flexible cardiac coil. Quantitative results from the patient study agreed well with the phantom findings. ConclusionsWe presented and validated an accurate method to localize and register a CT-based attenuation map to correct for the attenuation and scatter of flexible MR coils. This method may be translated to clinical use to produce quantitatively accurate measurements with the use of flexible MR coils during MR/PET imaging.

Markerless attenuation correction for carotid MRI surface receiver coils in combined PET/MR imaging.

The purpose of the study was to evaluate the effect of attenuation of MR coils on quantitative carotid PET/MR exams. Additionally, an automated attenuation correction method for flexible carotid MR coils was developed and evaluated. The attenuation of the carotid coil was measured by imaging a uniform water phantom injected with 37 MBq of 18F-FDG in a combined PET/MR scanner for 24 min with and without the coil. In the same session, an ultra-short echo time (UTE) image of the coil on top of the phantom was acquired. Using a combination of rigid and non-rigid registration, a CT-based attenuation map was registered to the UTE image of the coil for attenuation and scatter correction. After phantom validation, the effect of the carotid coil attenuation and the attenuation correction method were evaluated in five subjects. Phantom studies indicated that the overall loss of PET counts due to the coil was 6.3% with local region-of-interest (ROI) errors reaching up to 18.8%. Our registration method to correct for attenuation from the coil decreased the global error and local error (ROI) to 0.8% and 3.8%, respectively. The proposed registration method accurately captured the location and shape of the coil with a maximum spatial error of 2.6 mm. Quantitative analysis in human studies correlated with the phantom findings, but was dependent on the size of the ROI used in the analysis. MR coils result in significant error in PET quantification and thus attenuation correction is needed. The proposed strategy provides an operator-free method for attenuation and scatter correction for a flexible MRI carotid surface coil for routine clinical use.

SHILO, a novel dual imaging approach for simultaneous HI-/LOw temporal (Low-/Hi-spatial) resolution imaging for vascular dynamic contrast enhanced cardiovascular magnetic resonance: numerical simulations and feasibility in the carotid arteries

BackgroundDynamic contrast enhanced (DCE) cardiovascular magnetic resonance (CMR) is increasingly used to quantify microvessels and permeability in atherosclerosis. Accurate quantification depends on reliable sampling of both vessel wall (VW) uptake and contrast agent dynamic in the blood plasma (the so called arterial input function, AIF). This poses specific challenges in terms of spatial/temporal resolution and matched dynamic MR signal range, which are suboptimal in current vascular DCE-CMR protocols. In this study we describe a novel dual-imaging approach, which allows acquiring simultaneously AIF and VW images using different spatial/temporal resolution and optimizes imaging parameters for the two compartments. We refer to this new acquisition as SHILO, Simultaneous HI-/LOw-temporal (low-/hi-spatial) resolution DCE-imaging.MethodsIn SHILO, the acquisition of low spatial resolution single-shot AIF images is interleaved with segments of higher spatial resolution images of the VW. This allows sampling the AIF and VW with different spatial/temporal resolution and acquisition parameters, at independent spatial locations. We show the adequacy of this temporal sampling scheme by using numerical simulations. Following, we validate the MR signal of SHILO against a standard 2D spoiled gradient recalled echo (SPGR) acquisition with in vitro and in vivo experiments. Finally, we show feasibility of using SHILO imaging in subjects with carotid atherosclerosis.ResultsOur simulations confirmed the superiority of the SHILO temporal sampling scheme over conventional strategies that sample AIF and tissue curves at the same time resolution. Both the median relative errors and standard deviation of absolute parameter values were lower for the SHILO than for conventional sampling schemes. We showed equivalency of the SHILO signal and conventional 2D SPGR imaging, using both in vitro phantom experiments (R2 =0.99) and in vivo acquisitions (R2 =0.95). Finally, we showed feasibility of using the newly developed SHILO sequence to acquire DCE-CMR data in subjects with carotid atherosclerosis to calculate plaque perfusion indices.ConclusionsWe successfully demonstrate the feasibility of using the newly developed SHILO dual-imaging technique for simultaneous AIF and VW imaging in DCE-CMR of atherosclerosis. Our initial results are promising and warrant further investigation of this technique in wider studies measuring kinetic parameters of plaque neovascularization with validation against gold standard techniques.

Clinical Utility of Combined FDG-PET/MR to Assess Myocardial Disease

The assessment of both the pattern and activity of myocardial injury has important implications for the clinical management of patients with cardiovascular disease. Comprehensive evaluation of these has previously been challenging using a single imaging modality. Cardiac magnetic resonance (CMR)

Simultaneous carotid PET/MR: feasibility and improvement of magnetic resonance-based attenuation correction

Errors in quantification of carotid positron emission tomography (PET) in simultaneous PET/magnetic resonance (PET/MR) imaging when not incorporating bone in MR-based attenuation correction (MRAC) maps, and possible solutions, remain to be fully explored. In this study, we demonstrated techniques to improve carotid vascular PET/MR quantification by adding a bone tissue compartment to MRAC maps and deriving continuous Dixon-based MRAC (MRACCD) maps. We demonstrated the feasibility of applying ultrashort echo time-based bone segmentation and generation of continuous Dixon MRAC to improve PET quantification on five subjects. We examined four different MRAC maps: system standard PET/MR MRAC map (air, lung, fat, soft tissue) (MRACPET/MR), standard PET/MR MRAC map with bone (air, lung, fat, soft tissue, bone) (MRACPET/MRUTE), MRACCD map (no bone) and continuous Dixon-based MRAC map with bone (MRACCDUTE). The same PET emission data was then reconstructed with each respective MRAC map and a CTAC map (PETPET/MR, PETPET/MRUTE, PETCD, PECDUTE) to assess effects of the different attenuation maps on PET quantification in the carotid arteries and neighboring tissues. Quantitative comparison of MRAC attenuation values for each method compared to CTAC showed small differences in the carotid arteries with UTE-based segmentation of bone included and/or continuous Dixon MRAC; however, there was very good correlation for all methods in the voxel-by-voxel comparison. ROI-based analysis showed a similar trend in the carotid arteries with the lowest correlation to PETCTAC being PETPETMR and the highest correlation to PETCTAC being PETCDUTE. We have demonstrated the feasibility of applying UTE-based segmentation and continuous Dixon MRAC maps to improve carotid PET/MR vascular quantification.

MR/PET Imaging of the Cardiovascular System

Cardiovascular imaging has largely focused on identifying structural, functional, and metabolic changes in the heart. The ability to reliably assess disease activity would have major potential clinical advantages, including the identification of early disease, differentiating active from stable conditions, and monitoring disease progression or response to therapy. Positron emission tomography (PET) imaging now allows such assessments of disease activity to be acquired in the heart, whereas magnetic resonance (MR) scanning provides detailed anatomic imaging and tissue characterization. Hybrid MR/PET scanners therefore combine the strengths of 2 already powerful imaging modalities. Simultaneous acquisition of the 2 scans also provides added benefits, including improved scanning efficiency, motion correction, and partial volume correction. Radiation exposure is lower than with hybrid PET/computed tomography scanning, which might be particularly beneficial in younger patients who may need repeated scans. The present review discusses the expanding clinical literature investigating MR/PET imaging, highlights its advantages and limitations, and explores future potential applications.