‘Image-navigated 3-dimensional late gadolinium enhancement cardiovascular magnetic resonance imaging: feasibility and initial clinical results’

Background

Image-navigated 3-dimensional late gadolinium enhancement (iNAV-3D LGE) is an advanced imaging technique that allows for direct respiratory motion correction of the heart. Its feasibility in a routine clinical setting has not been validated.

Methods

Twenty-three consecutive patients referred for cardiovascular magnetic resonance (CMR) examination including late gadolinium enhancement (LGE) imaging were prospectively enrolled. Image-navigated free-breathing 3-dimensional (3D) T1-weighted gradient-echo LGE and two-dimensional (2D LGE) images were acquired in random order on a 1.5 T CMR system. Images were assessed for global, segmental LGE detection and transmural extent. Objective image quality including signal-to-noise (SNR), contrast-to-noise (CNR) and myocardial/blood sharpness were performed.

Results

Interpretable images were obtained in all 2D–LGE and in 22/23 iNAV-3D LGE exams, resulting in a total of 22 datasets and 352 segments. LGE was detected in 5 patients with ischemic pattern, in 7 with non-ischemic pattern, while it was absent in 10 cases. There was an excellent agreement between 2D and 3D data sets with regard to global, segmental LGE detection and transmurality. Blood-myocardium sharpness measurements were also comparable between the two techniques. SNR_blood and CNR_blood-myo was significantly higher for 2D LGE (P?<?0.001, respectively), while SNR_myo was not statistically significant between 2D LGE and iNAV-3D LGE.

Conclusion

Diagnostic performance of iNAV-3D LGE was comparable to 2D LGE in a prospective clinical setting. SNR_blood and CNR_blood-myo was significantly lower in the iNAV-3D LGE group.

     

3D whole-heart phase sensitive inversion recovery CMR for simultaneous black-blood late gadolinium enhancement and bright-blood coronary CMR angiography

Background

Phase sensitive inversion recovery (PSIR) applied to late gadolinium enhancement (LGE) imaging is widely used in clinical practice. However, conventional 2D PSIR LGE sequences provide sub-optimal contrast between scar tissue and blood pool, rendering the detection of subendocardial infarcts and scar segmentation challenging. Furthermore, the acquisition of a low flip angle reference image doubles the acquisition time without providing any additional diagnostic information. The purpose of this study was to develop and test a novel 3D whole-heart PSIR-like framework, named BOOST, enabling simultaneous black-blood LGE assessment and bright-blood visualization of cardiac anatomy.

Methods

The proposed approach alternates the acquisition of a 3D volume preceded by a T₂-prepared Inversion Recovery (T₂Prep-IR) module (magnitude image) with the acquisition of a T₂-prepared 3D volume (reference image). The two volumes (T₂Prep-IR BOOST and bright-blood T₂Prep BOOST) are combined in a PSIR-like reconstruction to obtain a complementary 3D black-blood volume for LGE assessment (PSIR BOOST). The black-blood PSIR BOOST and the bright-blood T₂Prep BOOST datasets were compared to conventional clinical sequences for scar detection and coronary CMR angiography (CMRA) in 18 patients with a spectrum of cardiovascular disease (CVD).

Results

Datasets from 12 patients were quantitatively analysed. The black-blood PSIR BOOST dataset provided statistically improved contrast to noise ratio (CNR) between blood and scar when compared to a clinical 2D PSIR sequence (15.8 ± 3.3 and 4.1 ± 5.6, respectively). Overall agreement in LGE depiction was found between 3D black-blood PSIR BOOST and clinical 2D PSIR acquisitions, with 11/12 PSIR BOOST datasets considered diagnostic. The bright-blood T₂Prep BOOST dataset provided high quality depiction of the proximal coronary segments, with improvement of visual score when compared to a clinical CMRA sequence. Acquisition time of BOOST (~10 min), providing information on both LGE uptake and heart anatomy, was comparable to that of a clinical single CMRA sequence.

Conclusions

The feasibility of BOOST for simultaneous black-blood LGE assessment and bright-blood coronary angiography was successfully tested in patients with cardiovascular disease. The framework enables free-breathing multi-contrast whole-heart acquisitions with 100% scan efficiency and predictable scan time. Complementary information on 3D LGE and heart anatomy are obtained reducing examination time.

     

Simultaneous multi slice (SMS) balanced steady state free precession first-pass myocardial perfusion cardiovascular magnetic resonance with iterative reconstruction at 1.5 T

Background

Simultaneous-Multi-Slice (SMS) perfusion imaging has the potential to acquire multiple slices, increasing myocardial coverage without sacrificing in-plane spatial resolution. To maximise signal-to-noise ratio (SNR), SMS can be combined with a balanced steady state free precession (bSSFP) readout. Furthermore, application of gradient-controlled local Larmor adjustment (GC-LOLA) can ensure robustness against off-resonance artifacts and SNR loss can be mitigated by applying iterative reconstruction with spatial and temporal regularisation. The objective of this study was to compare cardiovascular magnetic resonance (CMR) myocardial perfusion imaging using SMS bSSFP imaging with GC-LOLA and iterative reconstruction to 3 slice bSSFP.

Methods

Two contrast-enhanced rest perfusion sequences were acquired in random order in 8 patients: 6-slice SMS bSSFP and 3 slice bSSFP. All images were reconstructed with TGRAPPA. SMS images were also reconstructed using a non-linear iterative reconstruction with L1 regularisation in wavelet space (SMS-iter) with 7 different combinations for spatial (λ_σ) and temporal (λ_τ) regularisation parameters. Qualitative ratings of overall image quality (0?=?poor image quality, 1?=?major artifact, 2?=?minor artifact, 3?=?excellent), perceived SNR (0?=?poor SNR, 1?=?major noise, 2?=?minor noise, 3?=?high SNR), frequency of sequence related artifacts and patient related artifacts were undertaken. Quantitative analysis of contrast ratio (CR) and percentage of dark rim artifact (DRA) was performed.

Results

Among all SMS-iter reconstructions, SMS-iter 6 (λ_σ 0.001 λ_τ 0.005) was identified as the optimal reconstruction with the highest overall image quality, least sequence related artifact and higher perceived SNR. SMS-iter 6 had superior overall image quality (2.50?±?0.53 vs 1.50?±?0.53, p?=?0.005) and perceived SNR (2.25?±?0.46 vs 0.75?±?0.46, p?=?0.010) compared to 3 slice bSSFP. There were no significant differences in sequence related artifact, CR (3.62?±?0.39 vs 3.66?±?0.65, p?=?0.88) or percentage of DRA (5.25?±?6.56 vs 4.25?±?4.30, p?=?0.64) with SMS-iter 6 compared to 3 slice bSSFP.

Conclusions

SMS bSSFP with GC-LOLA and iterative reconstruction improved image quality compared to a 3 slice bSSFP with doubled spatial coverage and preserved in-plane spatial resolution. Future evaluation in patients with coronary artery disease is warranted.

     

Optimized CEST cardiovascular magnetic resonance for assessment of metabolic activity in the heart

Background

Previous studies have linked cardiac dysfunction to loss of metabolites in the creatine kinase system. Chemical exchange saturation transfer (CEST) is a promising metabolic cardiovascular magnetic resonance (CMR) imaging technique and has been applied in the heart for creatine mapping. However, current limitations include: (a) long scan time, (b) residual cardiac and respiratory motion, and (c) B₀ field variations induced by respiratory motion. An improved CEST CMR technique was developed to address these problems.

Methods

Animals with chronic myocardial infarction (N?=?15) were scanned using the proposed CEST CMR technique and a late gadolinium enhancement (LGE)  sequence as reference. The major improvements of the CEST CMR technique are: (a) Images were acquired by single-shot FLASH, significantly increasing the scan efficiency. (b) All images were registered to reduce the residual motion. (c) The acquired Z-spectrum was analyzed using 3-pool-model Lorentzian-line fitting to generate CEST signal, reducing the impact of B₀ field shifting due to respiratory motion. Feasibility of the technique was tested in a porcine model with chronic myocardial infarction. CEST signal was measured in the scar, border zone and remote myocardium. Initial studies were performed in one patient.

Results

In all animals, healthy remote myocardial CEST signal was elevated (0.16?±?0.02) compared to infarct CEST signal (0.09?±?0.02, P?<?0.001) and the border zone (0.12?±?0.02, P?<?0.001). For both animal and patient studies, the hypointense regions in the CEST contrast maps closely match the bright areas in the LGE images.

Conclusions

The proposed CEST CMR technique was developed to address long scan times, respiratory and cardiac motion, and B₀ field variations. Lower CEST signal in bright region of the LGE image is consistent with the fact that myocardial infarction has reduced metabolic activity.

     

Real-time assessment of right and left ventricular volumes and function in children using high spatiotemporal resolution spiral bSSFP with compressed sensing

Background

Real-time cardiovascular magnetic resonance (CMR) assessment of ventricular volumes and function enables data acquisition during free-breathing. The requirement for high spatiotemporal resolution in children necessitates the use of highly accelerated imaging techniques.

Methods

A novel real-time balanced steady state free precession (bSSFP) spiral sequence reconstructed using Compressed Sensing (CS) was prospectively validated against the breath-hold clinical standard for assessment of ventricular volumes in 60 children with congenital heart disease. Qualitative image scoring, quantitative image quality, as well as evaluation of biventricular volumes was performed. Standard BH and real-time measures were compared using the paired t-test and agreement for volumetric measures were evaluated using Bland Altman analysis.

Results

Acquisition time for the entire short axis stack (~?13 slices) using the spiral real-time technique was ~?20 s, compared to ~?348 s for the standard breath hold technique. Qualitative scores reflected more residual aliasing artefact (p?<?0.001) and lower edge definition (p?<?0.001) in spiral real-time images than standard breath hold images, with lower quantitative edge sharpness and estimates of image contrast (p?<?0.001).There was a small but statistically significant (p?<?0.05) overestimation of left ventricular (LV) end-systolic volume (1.0?±?3.5 mL), and underestimation of LV end-diastolic volume (??1.7?±?4.6 mL), LV stroke volume (??2.6?±?4.8 mL) and LV ejection fraction (??1.5?±?3.0%) using the real-time technique. We also observed a small underestimation of right ventricular stroke volume (??1.8?±?4.9 mL) and ejection fraction (??1.4?±?3.7%) using the real-time imaging technique. No difference in inter-observer or intra-observer variability were observed between the BH and real-time sequences.

Conclusions

Real-time bSSFP imaging using spiral trajectories combined with a compressed sensing reconstruction showed good agreement for quantification of biventricular metrics in children with heart disease, despite slightly lower image quality. This technique holds the potential for free breathing data acquisition, with significantly shorter scan times in children.

     

Maldistribution of pulmonary blood flow in patients after the Fontan operation is associated with worse exercise capacity

Background

Maldistribution of pulmonary artery blood flow (MPBF) is a potential complication in patients who have undergone single ventricle palliation culminating in the Fontan procedure. Cardiovascular magnetic resonance (CMR) is the best modality that can evaluate MPBF in this population. The purpose of this study is to identify the prevalence and associations of MPBF and to determine the impact of MPBF on exercise capacity after the Fontan operation.

Methods

This retrospective single-center study included all patients after Fontan operation who had maximal cardiopulmonary exercise test (CPET) and CMR with flow measurements of the branch pulmonary arteries. MPBF was defined as >?20% difference in branch pulmonary artery flow. Exercise capacity was measured as percent of predicted oxygen consumption at peak exercise (% predicted VO₂). Linear and logistic regression models were used to determine univariate and multivariable predictors of exercise capacity and correlates of MPBF, respectively.

Results

A total of 147 patients who had CMR between 1999 and 2017 were included (median age at CMR 21.8?years [interquartile range (IQR) 16.5–30.6]) and the median time between CMR and CPET was 2.8?months [IQR 0–13.8]. Fifty-three patients (36%) had MPBF (95% CI 29–45%). The mean % predicted VO₂ was 63?±?16%. Patients with MPBF had lower mean % predicted VO₂ compared to patients without MPBF (60?±?14% versus 65?±?16%, p?=?0.04). On multivariable analysis, a lower % predicted VO₂ was independently associated with longer time since Fontan, higher ventricular mass-to-volume ratio, and MPBF. On multivariable analysis, only compression of the branch pulmonary arteries by the ascending aorta or aortic root was associated with MPBF (OR 6.5, 95% CI 5.6–7.4, p?<?0.001).

Conclusion

In patients after the Fontan operation, MPBF is common and is independently associated with lower exercise capacity. MPBF was most likely to be caused by pulmonary artery compression by the aortic root or the ascending aorta. This study identifies MPBF as an important risk factor and as a potential target for therapeutic interventions in this fragile patient population.

     

Regional assessment of carotid artery pulse wave velocity using compressed sensing accelerated high temporal resolution 2D CINE phase contrast cardiovascular magnetic resonance

Background

Cardiovascular magnetic resonance (CMR) allows for non-invasive assessment of arterial stiffness by means of measuring pulse wave velocity (PWV). PWV can be calculated from the time shift between two time-resolved flow curves acquired at two locations within an arterial segment. These flow curves can be derived from two-dimensional CINE phase contrast CMR (2D CINE PC CMR). While CMR-derived PWV measurements have proven to be accurate for the aorta, this is more challenging for smaller arteries such as the carotids due to the need for both high spatial and temporal resolution. In this work, we present a novel method that combines retrospectively gated 2D CINE PC CMR, high temporal binning of data and compressed sensing (CS) reconstruction to accomplish a temporal resolution of 4 ms. This enables accurate flow measurements and assessment of PWV in regional carotid artery segments.

Methods

Retrospectively gated 2D CINE PC CMR data acquired in the carotid artery was binned into cardiac frames of 4 ms length, resulting in an incoherently undersampled k_y-t-space with a mean undersampling factor of 5. The images were reconstructed by a non-linear CS reconstruction using total variation over time as a sparsifying transform. PWV values were calculated from flow curves by using foot-to-foot and cross-correlation methods. Our method was validated against ultrasound measurements in a flow phantom setup representing the carotid artery. Additionally, PWV values of two groups of 23 young (30?±?3 years, 12 [52%] women) and 10 elderly (62?±?10 years, 5 [50%] women) healthy subjects were compared using the Wilcoxon rank-sum test.

Results

Our proposed method produced very similar flow curves as those measured using ultrasound at 1 ms temporal resolution. Reliable PWV estimation proved possible for transit times down to 7.5 ms. Furthermore, significant differences in PWV values between healthy young and elderly subjects were found (4.7?±?1.0 m/s and 7.9?±?2.4 m/s, respectively; p?<?0.001) in accordance with literature.

Conclusions

Retrospectively gated 2D CINE PC CMR with CS allows for high spatiotemporal resolution flow measurements and accurate regional carotid artery PWV calculations. We foresee this technique will be valuable in protocols investigating early development of carotid atherosclerosis.

     

Ferumoxytol enhanced black-blood cardiovascular magnetic resonance imaging

Background

Bright-blood and black-blood cardiovascular magnetic resonance (CMR) techniques are frequently employed together during a clinical exam because of their complementary features. While valuable, existing black-blood CMR approaches are flow dependent and prone to failure. We aim to assess the effectiveness and reliability of ferumoxytol enhanced (FE) Half-Fourier Single-shot Turbo Spin-echo (HASTE) imaging without magnetization preparation pulses to yield uniform intra-luminal blood signal suppression by comparing FE-HASTE with pre-ferumoxytol HASTE imaging.

Methods

This study was IRB-approved and HIPAA compliant. Consecutive patients who were referred for FE-CMR between June 2013 and February 2017 were enrolled. Qualitative image scores reflecting the degree and reliability of blood signal suppression were based on a 3-point Likert scale, with 3 reflecting perfect suppression. For quantitative evaluation, homogeneity indices (defined as standard deviation of the left atrial signal intensity) and signal-to-noise ratios (SNR) for vascular lumens and cardiac chambers were measured.

Results

Of the 340 unique patients who underwent FE-CMR, HASTE was performed in 257. Ninety-three patients had both pre-ferumoxytol HASTE and FE-HASTE, and were included in this analysis. Qualitative image scores reflecting the degree and reliability of blood signal suppression were significantly higher for FE-HASTE images (2.9 [IQR 2.8–3.0] vs 1.8 [IQR 1.6–2.1], p?<?0.001). Inter-reader agreement was moderate (k?=?0.50, 95% CI 0.45–0.55). Blood signal suppression was more complete on FE-HASTE images than on pre-ferumoxytol HASTE, as indicated by lower mean homogeneity indices (24.5 [IQR 18.0–32.8] vs 108.0 [IQR 65.0–170.4], p?<?0.001) and lower blood pool SNR for all regions (5.6 [IQR 3.2–10.0] vs 21.5 [IQR 12.5–39.4], p?<?0.001).

Conclusion

FE-HASTE black-blood imaging offers an effective, reliable, and simple approach for flow independent blood signal suppression. The technique holds promise as a fast and routine complement to bright-blood cardiovascular imaging with ferumoxytol.

     

Advances in Quantitative Tissue Characterization in Myocarditis

Purpose of Review

Myocarditis is a heterogeneous disease with variable histologic and clinical presentation. Cardiovascular magnetic resonance (CMR) imaging recently emerged as the imaging modality of choice in myocarditis. This review summarizes recent findings and future directions in this field.

Recent Findings

Advanced quantitative T1 mapping and T2 mapping methods have the technical advantage to detect diffuse myocardial injury in myocarditis, which was not adequately addressed by standard, semiquantitative CMR techniques so far. Recent studies demonstrated that the technical advantages of T1 and T2 mapping techniques improve the diagnostic accuracy and assessment of disease activity in myocarditis compared to standard CMR techniques using the Lake Louise Criteria for a CMR-based diagnosis of myocarditis.

Summary

Quantitative tissue characterization by T1 and T2 mapping techniques will further enhance the value of CMR in myocarditis.

     

The interplay between metabolic alterations,diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study

Background

Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.

Methods

Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent ¹H-cardiovascular magnetic resonance spectroscopy (¹H-CMRS) to measure MTG (lipid/water, %), ³¹P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.

Results

When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45?±?0.25% vs. 0.64?±?0.16%, p?=?0.009) and reduced PCr/ATP (1.60?±?0.09 vs. 2.00?±?0.10, p?=?0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO₂ max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO₂ max.

Conclusions

Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.

     

Automatic adjustment of pressure support by a computer-driven knowledge-based system during noninvasive ventilation: a feasibility study

Objective

To evaluate the feasibility of using a knowledge-based system designed to automatically titrate pressure support (PS) to maintain the patient in a “respiratory comfort zone” during noninvasive ventilation (NIV) in patients with acute respiratory failure.

Design and setting

Prospective crossover interventional study in an intensive care unit of a university hospital.

Patients

Twenty patients.

Interventions

After initial NIV setting and startup in conventional PS by the chest physiotherapist NIV was continued for 45?min with the automated PS activated.

Measurements and results

During automated PS minute-volume was maintained constant while respiratory rate decreased significantly from its pre-NIV value (20?±?3 vs. 25?±?3?bpm). There was a trend towards a progressive lowering of dyspnea. In hypercapnic patients PaCO₂ decreased significantly from 61?±?9 to 51?±?2?mmHg, and pH increased significantly from 7.31?±?0.05 to 7.35?±?0.03. Automated PS was well tolerated. Two system malfunctions occurred prompting physiotherapist intervention.

Conclusions

The results of this feasibility study suggest that the system can be used during NIV in patients with acute respiratory failure. Further studies should now determine whether it can improve patient-ventilator interaction and reduce caregiver workload.

     

Pooled Aquablation Results for American Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia in Large Prostates (60–150 cc)

Introduction

To present short-term safety and efficacy data of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) treated with Aquablation.

Methods

Men with LUTs secondary to BPH (60–150 cc) underwent Aquablation treatment from February 2016 to December 2017 across 17 investigational sites in the USA from two contemporary investigational device exemption (IDE) studies called WATER (NCT02505919) and WATER II (NCT03123250).

Results

One hundred seven males with mean age of 67.3?±?6.5 years were treated with Aquablation; mean prostate volume was 99.4?±?24.1 cc. The pooled results show that large prostates have an average procedure time of less than 36 min and discharge on average 1.6?±?1 days. The IPSS decreased by 16.7?±?8.1 points at 3 months and Q_max increased by 11.2?±?12.4 ml/s. The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown for CD events yielded 18% grade 2 and 19% grade 3 or higher.

Conclusion

Men with LUTS secondary to BPH (60–150 cc) in a pooled analysis were treated safely and effectively with Aquablation up to 3 months postoperatively.

Trial Registration

ClinicalTrials.gov identifiers, NCT02505919 and NCT03123250.

Funding

PROCEPT BioRobotics.

     

Effects of caffeine on the detection of ischemia in patients undergoing adenosine stress cardiovascular magnetic resonance imaging

Background

Adenosine stress cardiovascular magnetic resonance (CMR) can detect significant coronary artery stenoses with high diagnostic accuracy. Caffeine is a nonselective competitive inhibitor of adenosine2A-receptors, which might hamper the vasodilator effect of adenosine stress, potentially yielding false-negative results. Much controversy exists about the influence of caffeine on adenosine myocardial perfusion imaging. Our study sought to investigate the effects of caffeine on ischemia detection in patients with suspected or known coronary artery disease (CAD) undergoing adenosine stress CMR.

Methods

Thirty patients with evidence of myocardial ischemia on caffeine-naïve adenosine stress CMR were prospectively enrolled and underwent repeat adenosine stress CMR after intake of 200 mg caffeine. Both CMR exams were then compared for evaluation of ischemic burden.

Results

Despite intake of caffeine, no conversion of a positive to a negative stress study occurred on a per patient basis. Although we found significant lower ischemic burden in CMR exams with caffeine compared to caffeine-naïve CMR exams, absolute differences varied only slightly (1 segment based on a 16-segment model, 3 segments on a 60-segment model, and 1 ml in total ischemic myocardial volume, p?<?0.001 each). Moreover, no relevant ischemia (≥2 segments in a 16-segment model) was missed by prior ingestion of caffeine.

Conclusions

Although differences were small and no relevant myocardial ischemia had been missed, prior consumption of caffeine led to significant reduction of ischemic burden, and might lower the high diagnostic and prognostic value of adenosine stress CMR. Therefore, we suggest that patients should still refrain from caffeine prior adenosine stress CMR tests.

     

Characterizing Cardiac Involvement in Chronic Kidney Disease Using CMR—a Systematic Review

Purpose of Review

The aim of the review was to identify and describe recent advances (over the last 3 years) in cardiac magnetic resonance (CMR) imaging in patients with chronic kidney disease (CKD). We conducted a literature review in line with current guidelines.

Recent Findings

The authors identified 22 studies. Patients with CKD had left ventricular global and regional dysfunction and adverse remodeling. Stress testing with CMR revealed a reduced stress-response in CKD patients. Native T1 relaxation times (as a surrogate markers of fibrosis) are elevated in CKD patients, proportional to disease duration. Patients with CKD have reduced strain magnitudes and reduced aortic distensibility.

Summary

CMR has diagnostic utility to identify and characterize cardiac involvement in this patient group. A number of papers have described novel findings over the last 3 years, suggesting that CMR has potential to become more widely used in studies in this patient group.

     

Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

Purpose

The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer.

Procedures

CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated in a xenograft breast cancer mouse model using ductal carcinoma in situ cells (DCIS).

Results

Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody into mice with DCIS xenografts overexpressing CAIX showed after 2 h a mean tumor-to-normal tissue ratio (TNR) of 4.3?±?0.6, compared to a TNR of 1.4?±?0.2 in mice injected with the negative control nanobody R2-IR. In DCIS mice, a TNR of 1.8?±?0.1 was obtained. Biodistribution studies demonstrated an uptake of 14.0?±?1.1 %I.D./g in DCIS?+?CAIX tumors, 4.6?±?0.8 %I.D./g in DCIS tumors, while 2.0?±?0.2 %I.D./g was obtained with R2-IR.

Conclusions

These results demonstrate the successful generation of a CAIX-specific nanobody-IRDye800CW conjugate that can be used for rapid imaging of (pre-)invasive breast cancer.

     

Quantitative Tissue Characterization in Pediatric Cardiology

Purpose of Review

This review discusses the cardiovascular magnetic resonance (CMR) myocardial tissue characterization techniques and its applications with a focus on pediatric patients. Delayed enhancement CMR (DE-CMR) is well established to detect focal myocardial fibrosis in the clinical setting but has its limitation in detecting diffuse myocardial disease. Newer mapping techniques allow exact assessment of myocardial relaxation times and their changes in various cardiac pathologies.

Recent Findings

T1 mapping gives new insights in diffuse myocardial disease in pediatric patients with tetralogy of Fallot. T2 mapping seems to be superior to other CMR parameters for identifying myocarditis. Changes in myocardial T2* in thalassemia major can be detected in childhood suggesting that myocardial damage occurs early in life.

Summary

Advanced CMR mapping techniques underlie a rapid development and enable a noninvasive characterization of the myocardium. Although data for young patients are limited, mapping techniques have the potential to become key imaging tools in pediatric patients.

     

Determination of functional residual capacity by oxygen washin-washout: a validation study

Objective

To validate a new system for functional residual capacity (FRC) measurements using oxygen washin/washout in spontaneously breathing humans. The system (LUFU, Drägerwerk AG, Lübeck, Germany) consists of an unmodified EVITA 4 ventilator, a side-stream paramagnetic oxygen sensor and a dedicated software.

Design

Laboratory study and measurements in spontaneously breathing volunteers.

Setting

Pulmonary function laboratory of a university hospital.

Participants

20 healthy and 15 lung diseased volunteers.

Interventions

FRC was measured by LUFU (LUFU-FRC) and by helium dilution (He-FRC); intra-thoracic gas volume (ITGV) was determined by body plethysmography. Each measurement cycle consisted of four independent LUFU-FRC determinations (step change of FiO₂ from 0.21 to 0.5 and back and from 0.21 to 1.0 and back), two helium-dilution runs and two body box measurements. Repeatability and agreement between methods were determined by comparing different measurements of one technique and by comparing different techniques among each other.

Measurements and results

Repeatability of LUFU-FRC was estimated by comparing washin to washout and the different FiO₂steps. The difference of the means was 3.7% at the most. Agreement between methods resulted in the following differences (mean?±?standard deviation of differences) for healthy and lung-diseased volunteers, respectively: LUFU-FRC vs. He-FRC –0.40?±?0.50?L (0.02?±?0.95?L), LUFU-FRC vs. ITGV –0.43?±?0.54?L (–0.18?±?0.61?L) and He-FRC vs. ITGV –0.03?±?0.43?L (–0.20?±?0.98?L).

Conclusions

LUFU is a non-invasive method for the determination of FRC that requires only minor additional equipment and no modification to the ventilator. It can be used in difficult conditions such as breathing patterns with variations from breath to breath. The results of this study show that LUFU is sufficiently reliable and repeatable to warrant its clinical application.

     

Diagnostic performance of semi-quantitative and quantitative stress CMR perfusion analysis: a meta-analysis

Background

Stress cardiovascular magnetic resonance (CMR) perfusion imaging is a promising modality for the evaluation of coronary artery disease (CAD) due to high spatial resolution and absence of radiation. Semi-quantitative and quantitative analysis of CMR perfusion are based on signal-intensity curves produced during the first-pass of gadolinium contrast. Multiple semi-quantitative and quantitative parameters have been introduced. Diagnostic performance of these parameters varies extensively among studies and standardized protocols are lacking. This study aims to determine the diagnostic accuracy of semi- quantitative and quantitative CMR perfusion parameters, compared to multiple reference standards.

Method

Pubmed, WebOfScience, and Embase were systematically searched using predefined criteria (3272 articles). A check for duplicates was performed (1967 articles). Eligibility and relevance of the articles was determined by two reviewers using pre-defined criteria. The primary data extraction was performed independently by two researchers with the use of a predefined template. Differences in extracted data were resolved by discussion between the two researchers. The quality of the included studies was assessed using the ‘Quality Assessment of Diagnostic Accuracy Studies Tool’ (QUADAS-2). True positives, false positives, true negatives, and false negatives were subtracted/calculated from the articles. The principal summary measures used to assess diagnostic accuracy were sensitivity, specificity, andarea under the receiver operating curve (AUC). Data was pooled according to analysis territory, reference standard and perfusion parameter.

Results

Twenty-two articles were eligible based on the predefined study eligibility criteria. The pooled diagnostic accuracy for segment-, territory- and patient-based analyses showed good diagnostic performance with sensitivity of 0.88, 0.82, and 0.83, specificity of 0.72, 0.83, and 0.76 and AUC of 0.90, 0.84, and 0.87, respectively. In per territory analysis our results show similar diagnostic accuracy comparing anatomical (AUC 0.86(0.83–0.89)) and functional reference standards (AUC 0.88(0.84–0.90)). Only the per territory analysis sensitivity did not show significant heterogeneity. None of the groups showed signs of publication bias.

Conclusions

The clinical value of semi-quantitative and quantitative CMR perfusion analysis remains uncertain due to extensive inter-study heterogeneity and large differences in CMR perfusion acquisition protocols, reference standards, and methods of assessment of myocardial perfusion parameters. For wide spread implementation, standardization of CMR perfusion techniques is essential.

Trial registration

CRD42016040176.

     

Advanced Cardiovascular Magnetic Resonance Techniques in Grown-Up Congenital Heart Disease

Purpose

Congenital heart diseases comprise a complex population in which functional and anatomic evaluation with cardiac magnetic resonance (CMR) acquires utmost importance in the decision-making process. The use of new CMR technologies can help us understand the physiopathology and improve risk stratification.

Recent Findings

Efforts towards a better understanding of the processes that underlie the occurrence of adverse events in these patients, mainly heart failure and arrhythmia, have been made in the last years. Early identification of subclinical myocardial involvement by means of detection of changes at the cellular level (fibrosis and extracellular expansion) or impaired ventricular mechanics (deformation techniques) is now possible thanks to late gadolinium enhancement/T1 mapping and strain respectively.

Summary

Preliminary studies suggest that the presence of fibrosis, either replacement or diffuse fibrosis, and the detection of impaired deformation parameters or significant dyssynchrony are related to outcomes. Assessment of intracardiac and great vessels flow with 4D flow imaging is an attractive research tool that offers a comprehensive evaluation of hemodynamic status and the possibility of obtaining new promising functional parameters.

     

Stress perfusion magnetic resonance imaging to detect coronary artery lesions in children

Background

Stress perfusion cardiovascular magnetic resonance (CMR) is used widely in adult ischemic heart disease, but data in children is limited. We sought to evaluate feasibility, accuracy and prognostic value of stress CMR in children with suspected coronary artery disease (CAD).

Methods

Stress CMR was reviewed from two pediatric centers over 5 years using a standard pharmacologic protocol. Wall motion abnormalities, perfusion deficits and late enhancement were correlated with coronary angiogram (CAG) when available, and clinical status at 1 year follow-up for major adverse cardiovascular events (MACE; coronary revascularization, non-fatal myocardial infarction and death due to CAD) was recorded.

Results

Sixty-four stress perfusion CMR studies in 48 children (10.9?±?4.8 years) using adenosine; 59 (92%) and dipyridamole; 5 (8%), were reviewed. Indications were Kawasaki disease (39%), post arterial switch operation (12.5%), post heart transplantation (12.5%), post anomalous coronary artery repair (11%), chest pain (11%), suspected myocarditis or CAD (3%), post coronary revascularization (3%), and others (8%). Twenty-six studies were performed under sedation. Of all studies performed, 66% showed no evidence of ischemia or infarction, 28% had perfusion deficits and 6% had late gadolinium enhancement (LGE) without perfusion deficit. Compared to CAG, the positive predictive value (PPV) of stress CMR was 80% with negative predictive value (NPV) of 88%. At 1 year clinical follow-up, the PPV and NPV of stress CMR to predict MACE were 78 and 98%.

Conclusion

Stress-perfusion CMR, in combination with LGE and wall motion-analysis is a feasible and an accurate method of diagnosing CAD in children. In difficult cases, it also helps guide clinical intervention by complementing conventional CAG with functional information.