Evolving Characteristics of Gadolinium-Based Contrast Agents for MR Imaging: A Systematic Review of the Importance of Relaxivity.

Gadolinium-based contrast agents (GBCAs) are widely and routinely used to enhance the diagnostic performance of magnetic resonance imaging and magnetic resonance angiography examinations. T1 relaxivity (r1) is the measure of their ability to increase signal intensity in tissues and blood on T1-weighted images at a given dose. Pharmaceutical companies have invested in the design and development of GBCAs with higher and higher T1 relaxivity values, and "high relaxivity" is a claim frequently used to promote GBCAs, with no clear definition of what "high relaxivity" means, or general concurrence about its clinical benefit. To understand whether higher relaxivity values translate into a material clinical benefit, well-designed, and properly powered clinical studies are necessary, while mere in vitro measurements may be misleading. This systematic review of relevant peer-reviewed literature provides high-quality clinical evidence showing that a difference in relaxivity of at least 40% between two GBCAs results in superior diagnostic efficacy for the higher-relaxivity agent when this is used at the same equimolar gadolinium dose as the lower-relaxivity agent, or similar imaging performance when used at a lower dose. Either outcome clearly implies a relevant clinical benefit. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Part II: Effect of different evaluation methods to the application of a computer-aided prostate MRI detection/diagnosis (CADe/CADx) device on reader performance.

INTRODUCTION: The construction and results of a multiple-reader multiple-case prostate MRI study are described and reported to illustrate recommendations for how to standardize artificial intelligence (AI) prostate studies per the review constituting Part I1. METHODS: Our previously reported approach was applied to review and report an IRB approved, HIPAA compliant multiple-reader multiple-case clinical study of 150 bi-parametric prostate MRI studies across 9 readers, measuring physician performance both with and without the use of the recently FDA cleared CADe/CADx software ProstatID. RESULTS: Unassisted reader AUC values ranged from 0.418 - 0.759, with AI assisted AUC values ranging from 0.507 - 0.787. This represented a statistically significant AUC improvement of 0.045 (α = 0.05). A free-response ROC (FROC) analysis similarly demonstrated a statistically significant increase in θ from 0.405 to 0.453 (α = 0.05). The standalone performance of ProstatID performed across all prostate tissues demonstrated an AUC of 0.929, while the standalone lesion level performance of ProstatID at all biopsied locations achieved an AUC of 0.710. CONCLUSION: This study applies and illustrates suggested reporting and standardization methods for prostate AI studies that will make it easier to understand, evaluate and compare between AI studies. Providing radiologists with the ProstatID CADe/CADx software significantly increased diagnostic performance as assessed by both ROC and free-response ROC metrics. Such algorithms have the potential to improve radiologist performance in the detection and localization of clinically significant prostate cancer.

Part I: prostate cancer detection, artificial intelligence for prostate cancer and how we measure diagnostic performance: a comprehensive review.

MRI has firmly established itself as a mainstay for the detection, staging and surveillance of prostate cancer. Despite its success, prostate MRI continues to suffer from poor inter-reader variability and a low positive predictive value. The recent emergence of Artificial Intelligence (AI) to potentially improve diagnostic performance shows great potential. Understanding and interpreting the AI landscape as well as ever-increasing research literature, however, is difficult. This is in part due to widely varying study design and reporting techniques. This paper aims to address this need by first outlining the different types of AI used for the detection and diagnosis of prostate cancer, next deciphering how data collection methods, statistical analysis metrics (such as ROC and FROC analysis) and end points/outcomes (lesion detection vs. case diagnosis) affect the performance and limit the ability to compare between studies. Finally, this work explores the need for appropriately enriched investigational datasets and proper ground truth, and provides guidance on how to best conduct AI prostate MRI studies. Published in parallel, a clinical study applying this suggested study design was applied to review and report a multiple-reader multiple-case clinical study of 150 bi-parametric prostate MRI studies across nine readers, measuring physician performance both with and without the use of a recently FDA cleared Artificial Intelligence software.1.

Efficacy of Whole-Blood Model of Gadolinium-Based Contrast Agent Relaxivity in Predicting Vascular MR Signal Intensity In Vivo.

BACKGROUND: Previous in vitro studies have described sub-linear longitudinal and heightened transverse H2 O relaxivities of gadolinium-based contrast agents (GBCAs) in blood due to their extracellular nature. However, in vivo validation is lacking. PURPOSE: Validate theory describing blood behavior of R1 and R2 * in an animal model. STUDY TYPE: Prospective, animal. ANIMAL MODEL: Seven swine (54-65 kg). FIELD STRENGTH/SEQUENCE: 1.5 T; time-resolved 3D spoiled gradient-recalled echo (SPGR) and quantitative Look-Locker and multi-echo fast field echo sequences. ASSESSMENT: Seven swine were each injected three times with 0.1 mmol/kg intravenous doses of one of three GBCAs: gadoteridol, gadobutrol, and gadobenate dimeglumine. Injections were randomized for rate (1, 2, and 3 mL/s) and order, during which time-resolved aortic 3D SPGR imaging was performed concurrently with aortic blood sampling via an indwelling catheter. Time-varying [GBCA] was measured by mass spectrometry of sampled blood. Predicted signal intensity (SI) was determined from a model incorporating sub-linear R1 and R2 * effects (whole-blood model) and simpler models incorporating linear R1 , with and without R2 * effects. Predicted SIs were compared to measured aortic SI. STATISTICAL TESTS: Linear correlation (coefficient of determination, R2 ) and mean errors were compared across the SI prediction models. RESULTS: There was an excellent correlation between predicted and measured SI across all injections and swine when accounting for the non-linear dependence of R1 and high blood R2 * (regression slopes 0.91-1.04, R2 ≥ 0.91). Simplified models (linear R1 with and without R2 * effects) showed poorer correlation (slopes 0.67-0.85 and 0.54-0.64 respectively, both R2 ≥ 0.89) and higher averaged mean absolute and mean square errors (128.4 and 177.4 vs. 42.0, respectively, and 5506 and 11,419 vs. 699, respectively). DATA CONCLUSION: Incorporating sub-linear R1 and high first-pass R2 * effects in arterial blood models allows accurate SPGR SI prediction in an in vivo animal model, and might be utilized when modeling MR blood SI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Near-Infrared Imaging of Indocyanine Green Identifies Novel Routes of Lymphatic Drainage from Metacarpophalangeal Joints in Healthy Human Hands.

Background: Collecting lymphatic vessel (CLV) dysfunction has been implicated in various diseases, including rheumatoid arthritis (RA). RA patients with active hand arthritis exhibit significantly reduced lymphatic clearance of the web spaces adjacent to the metacarpophalangeal (MCP) joints and a reduction in total and basilic-associated CLVs on the dorsal surface of the hand by near-infrared (NIR) imaging of indocyanine green (ICG). In this pilot study, we assessed direct lymphatic drainage from MCP joints and aimed to visualize the total lymphatic anatomy using novel dual-agent relaxation contrast magnetic resonance lymphography (DARC-MRL) in the upper extremity of healthy human subjects. Methods and Results: Two healthy male subjects >18 years old participated in the study. We performed NIR imaging along with conventional- or DARC-MRL following intradermal web space and intra-articular MCP joint injections. ICG (NIR) or gadolinium (Gd) (MRL) was administered to visualize the CLV anatomy of the upper extremity. Web space draining CLVs were associated with the cephalic side of the antecubital fossa, while MCP draining CLVs were localized to the basilic side of the forearm by near-infrared indocyanine green imaging. The DARC-MRL methods used in this study did not adequately nullify the contrast in the blood vessels, and limited Gd-filled CLVs were identified. Conclusion: MCP joints predominantly drain into basilic CLVs in the forearm, which may explain the reduction in basilic-associated CLVs in the hands of RA patients. Current DARC-MRL techniques show limited identification of healthy lymphatic structures, and further refinement in this technique is necessary. Clinical trial registration number: NCT04046146.

Metabolic activity diffusion imaging (MADI): I. Metabolic, cytometric modeling and simulations.

Evidence mounts that the steady-state cellular water efflux (unidirectional) first-order rate constant (kio [s-1 ]) magnitude reflects the ongoing, cellular metabolic rate of the cytolemmal Na+ , K+ -ATPase (NKA), c MRNKA (pmol [ATP consumed by NKA]/s/cell), perhaps biology's most vital enzyme. Optimal 1 H2 O MR kio determinations require paramagnetic contrast agents (CAs) in model systems. However, results suggest that the homeostatic metabolic kio biomarker magnitude in vivo is often too large to be reached with allowable or possible CA living tissue distributions. Thus, we seek a noninvasive (CA-free) method to determine kio in vivo. Because membrane water permeability has long been considered important in tissue water diffusion, we turn to the well-known diffusion-weighted MRI (DWI) modality. To analyze the diffusion tensor magnitude, we use a parsimoniously primitive model featuring Monte Carlo simulations of water diffusion in virtual ensembles comprising water-filled and -immersed randomly sized/shaped contracted Voronoi cells. We find this requires two additional, cytometric properties: the mean cell volume (V [pL]) and the cell number density (ρ [cells/µL]), important biomarkers in their own right. We call this approach metabolic activity diffusion imaging (MADI). We simulate water molecule displacements and transverse MR signal decays covering the entirety of b-space from pure water (ρ = V = 0; kio undefined; diffusion coefficient, D0 ) to zero diffusion. The MADI model confirms that, in compartmented spaces with semipermeable boundaries, diffusion cannot be described as Gaussian: the nanoscopic D (Dn ) is diffusion time-dependent, a manifestation of the "diffusion dispersion". When the "well-mixed" (steady-state) condition is reached, diffusion becomes limited, mainly by the probabilities of (1) encountering (ρ, V), and (2) permeating (kio ) cytoplasmic membranes, and less so by Dn magnitudes. Importantly, for spaces with large area/volume (A/V; claustrophobia) ratios, this can happen in less than a millisecond. The model matches literature experimental data well, with implications for DWI interpretations.

Metabolic activity diffusion imaging (MADI): II. Noninvasive, high-resolution human brain mapping of sodium pump flux and cell metrics.

We introduce a new 1 H2 O magnetic resonance approach: metabolic activity diffusion imaging (MADI). Numerical diffusion-weighted imaging decay simulations characterized by the mean cellular water efflux (unidirectional) rate constant (kio ), mean cell volume (V), and cell number density (ρ) are produced from Monte Carlo random walks in virtual stochastically sized/shaped cell ensembles. Because of active steady-state trans-membrane water cycling (AWC), kio reflects the cytolemmal Na+ , K+ ATPase (NKA) homeostatic cellular metabolic rate (c MRNKA ). A digital 3D "library" contains thousands of simulated single diffusion-encoded (SDE) decays. Library entries match well with disparate, animal, and human experimental SDE decays. The V and ρ values are consistent with estimates from pertinent in vitro cytometric and ex vivo histopathological literature: in vivo V and ρ values were previously unavailable. The library allows noniterative pixel-by-pixel experimental SDE decay library matchings that can be used to advantage. They yield proof-of-concept MADI parametric mappings of the awake, resting human brain. These reflect the tissue morphology seen in conventional MRI. While V is larger in gray matter (GM) than in white matter (WM), the reverse is true for ρ. Many brain structures have kio values too large for current, invasive methods. For example, the median WM kio is 22s-1 ; likely reflecting mostly exchange within myelin. The kio •V product map displays brain tissue c MRNKA variation. The GM activity correlates, quantitatively and qualitatively, with the analogous resting-state brain 18 FDG-PET tissue glucose consumption rate (t MRglucose ) map; but noninvasively, with higher spatial resolution, and no pharmacokinetic requirement. The cortex, thalamus, putamen, and caudate exhibit elevated metabolic activity. MADI accuracy and precision are assessed. The results are contextualized with literature overall homeostatic brain glucose consumption and ATP production/consumption measures. The MADI/PET results suggest different GM and WM metabolic pathways. Preliminary human prostate results are also presented.

Relationship Between Simulated Gadolinium-Based Contrast Agent Injection Profile and Achievable Resolution Metrics in Contrast-Enhanced Magnetic Resonance Angiography.

BACKGROUND: Contrast bolus variation during contrast-enhanced magnetic resonance angiography (CE-MRA) acquisition may lead to vessel blurring. PURPOSE: To combine knowledge of how contrast signal intensity (SI) evolves for different injection strategies with anatomically familiar parametric computer models to measure and visually assess the effects of a wide range of variables on modeled CE-MRA, and in doing so develop contrast rate injection guidelines. STUDY TYPE: Computer modeling. PHANTOM: Digital three-dimensional phantom consisting of orthogonal "aorta," 7 mm diameter "renal arteries" (with 57% and 86% diameter stenoses), and 7 mm diameter "superior mesenteric artery" (with 57% diameter stenosis). FIELD STRENGTH/SEQUENCE: One millimeter in-plane resolution arterial CE-MRA imaging at 3 T. ASSESSMENT: "Background" (time invariant) and "vascular" (time varying) components of the phantom were each Fourier transformed into the spatial frequency domain, the latter modulated by the SI evolution of a contrast bolus of varying "plateau" lengths and "tail" heights. Data are presented as surface plots of stenosis measurement error and blurring vs. a reference-standard injection. STATISTICAL TESTS: Descriptive. RESULTS: Shorter plateau lengths and lower tail heights resulted in increased measured stenosis error and blurring vs. the reference standard. Under a 44-second acquisition, full width half maximum stenosis error of the 86% stenosis with 25% plateau length and 25% tail height is 24% as compared to that from the reference standard. As plateau length and tail height approach 100%, stenosis error and blurring approach a floor defined by the MR acquisition's limitations. DATA CONCLUSION: We propose that to achieve minimal degradation with CE-MRA, one can create a contrast bolus with either 60% plateau and 50% tail height or 80% plateau with any tail. These considerations may well prove to be of practical importance, possibly via manipulating the tail by means of multiphasic contrast injections. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Development of a standardized MRI protocol for pancreas assessment in humans.

Magnetic resonance imaging (MRI) has detected changes in pancreas volume and other characteristics in type 1 and type 2 diabetes. However, differences in MRI technology and approaches across locations currently limit the incorporation of pancreas imaging into multisite trials. The purpose of this study was to develop a standardized MRI protocol for pancreas imaging and to define the reproducibility of these measurements. Calibrated phantoms with known MRI properties were imaged at five sites with differing MRI hardware and software to develop a harmonized MRI imaging protocol. Subsequently, five healthy volunteers underwent MRI at four sites using the harmonized protocol to assess pancreas size, shape, apparent diffusion coefficient (ADC), longitudinal relaxation time (T1), magnetization transfer ratio (MTR), and pancreas and hepatic fat fraction. Following harmonization, pancreas size, surface area to volume ratio, diffusion, and longitudinal relaxation time were reproducible, with coefficients of variation less than 10%. In contrast, non-standardized image processing led to greater variation in MRI measurements. By using a standardized MRI image acquisition and processing protocol, quantitative MRI of the pancreas performed at multiple locations can be incorporated into clinical trials comparing pancreas imaging measures and metabolic state in individuals with type 1 or type 2 diabetes.

MR Angiography Series: Fundamentals of Contrast-enhanced MR Angiography.

The Society for Magnetic Resonance Angiography (SMRA) is a group of researchers and clinicians who are passionate about the benefits of MR angiography (MRA) but understand its challenges. Their mission is to study MRA, continually improve and innovate for the benefit of patients, and most important, educate the medical community so they can take full advantage of the benefits of MRA and overcome its challenges. In support of that mission, the authors have created a series of self-learning modules on behalf of the SMRA to demystify MRA protocols and help the reader perform patient-friendly high-quality MRA on a routine basis in clinical practice. The full digital presentation is available online. ©RSNA, 2021.

Evaluation of four injection profiles for uniform contrast-enhanced signal intensity profiles in MR angiography.

BACKGROUND: Gadolinium concentration variation during acquisition of contrast-enhanced MR angiography (CE-MRA) may lead to artifacts. PURPOSE: To compare signal intensity (SI) profiles of four different contrast agent injection strategies during CE-MRA with the goal of minimizing SI variation during acquisition. STUDY TYPE: Prospective. SUBJECTS: Forty subjects randomized to receive one of four injection profiles of gadobenate dimeglumine (0.1 mmol/kg), either undiluted (0.5 M) or diluted to 40 ml total volume. Tested profiles: 1) nondiluted single-phase ("standard" NS; 1.6 ml/s), 2) diluted single-phase (DS; 1.6 ml/s), 3) diluted biphasic (DB; 9 ml @ 3.3 ml/s, 29 ml @ 1.4 ml/s), 4) patient-tailored protocol using linear prediction (DT). FIELD STRENGTH/SEQUENCE: Time-resolved SI measured at 3T with spoiled gradient echo sequences having analogous parameters to those of CE-MRA. ASSESSMENT: Plateau arrival time, rise time, duration, peak and tail SI, plateau quality (sum of squared residuals; SSR), average SI for each injection type derived were used. STATISTICAL TEST: Two-tailed t-test. RESULTS: Peak SI, arrival, and rise times were not significantly different between groups, excepting peak SI DB slightly > DS (P = 0.042). Duration of NS vs. the diluted groups was significantly shorter (all P < 0.0001), and DS duration was significantly shorter than that of DT and DB (NS 11.4 ± 3.5 vs. DS 22.9 ± 4.3, DB 25.4 ± 2.3, DT 28.3 ± 4.1 sec). Quality (SSR) of the 20-second plateau was significantly better for DS, DB, DT as compared with NS (all P < 0.001). DATA CONCLUSION: Three different strategies to power-inject diluted gadobenate dimeglumine targeting a 20-second plateau produced SI profiles with longer duration, more consistent plateau, and no significant loss in peak SI. Such injection profiles may provide more uniform SI during CE-MRA, potentially reducing blurring artifacts. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1808-1816.

Magnetic resonance angiography imaging of pulmonary embolism using agents with blood pool properties as an alternative to computed tomography to avoid radiation exposure.

PURPOSE: To evaluate the feasibility and accuracy of a combined magnetic resonance angiography (MRA) - magnetic resonance venography (MRV) protocol using contrast agents with blood pool properties, gadofosveset trisodium and gadobenate dimeglumine, in the evaluation of pulmonary embolus (PE) and deep venous thrombosis (DVT) as compared to the standard clinical reference imaging modalities; computed tomography pulmonary angiography (CTPA) and color-coded Duplex ultrasound (DUS). MATERIALS AND METHODS: This prospective clinical study recruited patients presenting to the emergency department with clinical suspicion for PE and scheduled for a clinically indicated CTPA. We performed both MRA of the chest for the evaluation of PE as well as MRV of the pelvis and thighs to evaluate for DVT using a single contrast injection. MRA-MRV data was compared to the clinical reference standard CTPA and DUS, respectively. RESULTS: A total of 40 patients were recruited. The results on a per-patient basis comparing MRA to CTPA for pulmonary embolus yielded 100% sensitivity and 97% specificity. There was a small subset of patients that underwent clinical DUS to evaluate for DVT, which demonstrated a sensitivity and specificity of 100% for MRV. CONCLUSIONS: This single-center, preliminary study using contrast agents with blood pool properties to perform a relatively rapid combined MRA-MRV exam to image for PE and above knee DVT shows potential as an alternative imaging choice to CTPA. Further large-scale, multicentre studies are warranted.

CT Detectability of Small Low-Contrast Hypoattenuating Focal Lesions: Iterative Reconstructions versus Filtered Back Projection.

Purpose To investigate performance in detectability of small (≤1 cm) low-contrast hypoattenuating focal lesions by using filtered back projection (FBP) and iterative reconstruction (IR) algorithms from two major CT vendors across a range of 11 radiation exposures. Materials and Methods A low-contrast detectability phantom consisting of 21 low-contrast hypoattenuating focal objects (seven sizes between 2.4 and 10.0 mm, three contrast levels) embedded into a liver-equivalent background was scanned at 11 radiation exposures (volume CT dose index range, 0.5-18.0 mGy; size-specific dose estimate [SSDE] range, 0.8-30.6 mGy) with four high-end CT platforms. Data sets were reconstructed by using FBP and varied strengths of image-based, model-based, and hybrid IRs. Sixteen observers evaluated all data sets for lesion detectability by using a two-alternative-forced-choice (2AFC) paradigm. Diagnostic performances were evaluated by calculating area under the receiver operating characteristic curve (AUC) and by performing noninferiority analyses. Results At benchmark exposure, FBP yielded a mean AUC of 0.79 ± 0.09 (standard deviation) across all platforms which, on average, was approximately 2% lower than that observed with the different IR algorithms, which showed an average AUC of 0.81 ± 0.09 (P = .12). Radiation decreases of 30%, 50%, and 80% resulted in similar declines of observer detectability with FBP (mean AUC decrease, -0.02 ± 0.05, -0.03 ± 0.05, and -0.05 ± 0.05, respectively) and all IR methods investigated (mean AUC decrease, -0.00 ± 0.05, -0.04 ± 0.05, and -0.04 ± 0.05, respectively). For each radiation level and CT platform, variance in performance across observers was greater than that across reconstruction algorithms (P = .03). Conclusion Iterative reconstruction algorithms have limited radiation optimization potential in detectability of small low-contrast hypoattenuating focal lesions. This task may be further complicated by a high degree of variation in radiologists' performances, seemingly exceeding real performance differences among reconstruction algorithms. © RSNA, 2018 Online supplemental material is available for this article.

Initial Clinical Experience with Dual-Agent Relaxation Contrast for Isolated Lymphatic Channel Mapping.

Purpose To evaluate the clinical performance of dual-agent relaxation contrast (DARC) magnetic resonance (MR) lymphangiography compared with that of conventional MR lymphangiography in the creation of isolated lymphatic maps in patients with secondary lymphedema. Materials and Methods This retrospective study was approved by the institutional review board. The diagnostic quality of 42 DARC MR lymphangiographic studies was compared with that of 42 conventional MR lymphangiographic studies. Two independent readers rated venous contamination as absent, mild, or moderate to severe. Interreader agreement on venous contamination grades was assessed by using the linearly weighted Cohen κ statistic. The Mann-Whitney U test was used to compare the distribution of grades at each station between conventional MR lymphangiography and DARC MR lymphangiography for each reader separately. Results DARC MR lymphangiography had significantly less venous contamination than did conventional MR lymphangiography (P < .001). The two radiologists rated venous contamination as moderate to severe in 64% (27 of 42) and 69% (29 of 42) of distal limbs, 23% (10 of 42) of midlimbs, and 2% (one of 42) and 9% (four of 42) of proximal limbs at conventional MR lymphangiography compared with 0% (0 of 42) of distal limbs, 2% (one of 42) of midlimbs, and 0% (0 of 42) of proximal limbs at DARC MR lymphangiography. Lymphatic signal was partially attenuated (median 45% decrease) when longer echo times were used for venous suppression, but it did not subjectively degrade diagnostic quality. Conclusion DARC MR lymphangiography yields isolated lymphatic maps through nulling of venous contamination, thereby simplifying diagnostic interpretation and communication with surgical colleagues. © RSNA, 2017.

3D true-phase polarity recovery with independent phase estimation using three-tier stacks based region growing (3D-TRIPS).

OBJECTIVES: A postprocessing technique termed 3D true-phase polarity recovery with independent phase estimation using three-tier stacks based region growing (3D-TRIPS) was developed, which directly reconstructs phase-sensitive inversion-recovery images without acquisition of phase-reference images. The utility of this technique is demonstrated in myocardial late gadolinium enhancement (LGE) imaging. MATERIALS AND METHODS: A data structure with three tiers of stacks was used for 3D-TRIPS to directly achieve reliable region growing for successful background-phase estimation. Fifteen patients undergoing postgadolinium 3D phase-sensitive inversion recovery (PSIR) cardiac LGE magnetic resonance imaging (MRI) were recruited, and 3D-TRIPS LGE reconstructions were compared with standard PSIR. Objective voxel-by-voxel comparison was performed. Additionally, blinded review by two radiologists compared scar visibility, clinical acceptability, voxel polarity error, or groups and blurring. RESULTS: 3D-TRIPS efficiently reconstructed postcontrast phase-sensitive myocardial LGE images. Objective analysis showed an average 95% voxel-by-voxel agreement between 3D-TRIPS and PSIR images. Blinded radiologist review demonstrated similar image quality between 3D-TRIPS and PSIR reconstruction. CONCLUSION: 3D-TRIPS provided similar image quality to PSIR for phase-sensitive myocardial LGE MRI reconstruction. 3D-TRIPS does not require acquisition of a reference image and can therefore be used to accelerate phase-sensitive LGE imaging.

Risk assessment of patients with clinical manifestations of cardiac sarcoidosis with positron emission tomography and magnetic resonance imaging.

BACKGROUND: Prior studies have shown that late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) and fluorodeoxyglucose (FDG) positron emission tomography (PET) confer incremental risk assessment in patients with cardiac sarcoidosis (CS). However, the incremental prognostic value of the combined use of LGE and FDG compared to either test alone has not been investigated, and this is the aim of the present study. METHODS: Retrospective observational study of 56 symptomatic patients with high clinical suspicion for CS who underwent LGE-CMR and FDG-PET and were followed for the occurrence of death and/or malignant ventricular arrhythmias (VA). RESULTS: The combination of PET and CMR yielded the following groups: 1) LGE-negative/normal-PET (n=20), 2) LGE-positive/abnormal-FDG (n=20), and 3) LGE-positive/normal FDG (n=16). After a median follow-up of 2.6years (IQR 1.2-4.1), 16 patients had events (7 deaths, 10 VA). All, but 1, events occurred in patients with LGE. LGE-positive/abnormal-FDG (7 events, HR 10.1 [95% CI 1.2-84]; P=0.03) and LGE-positive/normal-FDG (8 events, HR 13.3 [1.7-107]; P=0.015) patients had comparable risk of events compared to the reference LGE-negative/normal-PET group. In adjusted Cox-regression analysis, presence of LGE (HR 18.1 [1.8-178]; P=0.013) was the only independent predictor of events. CONCLUSION: CS patients with LGE alone or in association with FDG were at similar risk of future events, which suggests that outcomes may be driven by the presence of LGE (myocardial fibrosis) and not FDG (inflammation).

Current Concepts in the Surgical Management of Lymphedema.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Discuss the key points in diagnosing lymphedema. 2. Understand the imaging modalities that facilitate diagnosis and surgical planning. 3. Appreciate the indications for both physiologic and ablative procedures. 4. Recognize the potential role of lymphaticovenular anastomosis and vascularized lymph node transfer in the treatment of patients with lymphedema. SUMMARY: Lymphedema is an incurable disease caused by insufficient lymphatic drainage leading to abnormal accumulation of interstitial fluid within the soft tissues. Although this condition may result from a primary structural defect of the lymphatic system, most cases in developed countries are secondary to iatrogenic causes. The diagnosis of lymphedema can be made readily by performing a clinical history and physical examination and may be confirmed by imaging studies such as lymphoscintigraphy, magnetic resonance lymphangiography, or indocyanine green lymphangiography. Nonsurgical treatment continues to be the mainstay of lymphedema management. However, advances in microsurgical techniques have revolutionized surgical options for treating lymphedema, and emerging evidence suggests that reconstructive methods may be performed to restore lymphatic flow. Procedures such as lymphaticovenular anastomosis and vascularized lymph node transfer can potentially offer a more permanent solution to chronic lymphedema, and initial studies have demonstrated promising results.