New 4-D MRI imaging in utero helping detect congenital heart disease of a baby in pregnant mothers

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Researchers at King’s College London have developed a new method for helping detect congenital heart disease of a baby in pregnant mothers using MRI.

Existing in-utero approaches are compromised by fetal motion, but the novel method corrects the motion to present 4-D visualizations of the heart depicting major vessels and blood flow circulation.

With further development, the method could become a new tool for aiding diagnosis of congenital heart disease where conventional methods like ultrasound might fail.

For the first time, in a new paper published today in Nature Communications, researchers have been able to look at the fetal heart in four dimensions – the images are still 3-D but change through time as the heart beats.

Rather than just getting a snapshot of the heart, say a single picture, a series of images is taken allowing cardiologists to see the heart contracting and beating.

While this is standard for adult imaging, until now it has not been possible for the fetal heart because of the spontaneous movement of the baby and the rapid speed of its beating heart – twice as fast as an adult’s.

Researcher Dr. Tom Roberts, from King’s College London, said the 4-D volumes are achieved by stitching them together using mathematical motion-correction techniques and models.

“The results in the paper are exciting because no one has been able to look at the fetal heart using MRI in four dimensions like this,” he said.

“When we give these videos of the beating heart to the doctors, they are able to interact and examine the direction of blood flow instantly.”

“The heart is a pump. Our method is very beneficial because doctors can start to measure how much blood is pumped out with each heartbeat, which can be used to tell how effectively the heart is performing. We can measure the amount of blood going through the aorta and other major vessels, simultaneously. We can get new types of measurements that you weren’t able to do before in fetal MRI.”

Currently diagnosis of congenital heart disease (CHD) mainly focuses on whether the fetal heart has formed in an incorrect way, but with this new technology the researchers hope to measure how well the heart is performing as well.

CHD has a broad range of different pathologies. This means sometimes there are relatively straight forward heart diseases but there are also more complicated ones which can be quite difficult to diagnose with ultrasound which currently is the main tool used.

The challenge is that while fetal blood flow can be measured using ultrasound, the measurements can often be unreliable.

MRI measurements of blood flow are easily performed in adult hearts to help tell if the heart is beating efficiently or not, or whether a vessel might have some abnormal flow of blood.

“When we scan a fetus, it moves and wriggles around however it wants which can prevent you from measuring the blood flow in the tiny vessels,” Dr. Roberts said.

“In our work, we’ve developed methods to correct for this motion and build those 3-D movies where we can measure blood flow in any region or vessel of the fetal heart.”

“The great thing about MRI is that it can offer really detailed, high resolution images of the fetal heart. We can use MRI for looking at the tiny vessels in the fetal heart which may be no more than 5mm wide.”Dr. Tom Roberts said the team hopes the research will lead to improved care for babies born with congenital heart disease.

“If CHD is detected prior to birth, then doctors can prepare appropriate care immediately at birth, which can sometimes be life-saving. It also gives parents advance time to prepare, when otherwise the CHD might have been discovered at birth, which can be very stressful,” he said.

“We are trying to advance fetal cardiac MRI as a way of potentially improving outcomes in congenital heart disease, either by being able to offer a better diagnosis or being able to look for congenital heart disease at an earlier time during pregnancy.”

Second author and clinical senior lecturer in pediatric cardiology Kuberan Pushparajah said the clinical teams are very excited by the opportunities this will bring as this world leading innovation in fetal 4-D imaging is applied into clinic.

“The technical challenges that have been overcome by the team in this work represent a massive leap forward in the field of fetal cardiac MRI,” he said. “We will now be able to simultaneously study the heart structures and track blood flow through it as it beats using MRI for the very first time.”

“This is key in the assessment of congenital heart disease where the heart structures and connections are abnormal and can be very complex. This will help us better understand and diagnose congenital heart disease to improve patient care.”


CHALLENGES OF FETAL CARDIAC MRI
Several practical challenges exist when imaging the fetal heart with MRI. The size of major fetal vessels at full gestation is in the range of 5 to 10 mm in diameter, the width of the fetal ventricles is in the range of 10 to 30 mm,4 the duration of the fetal cardiac cycle is between 330 and 540 ms with a systolic period between 20 and 50 ms,5–7 and a relatively large field-of-view (260 to 480 mm) is required to avoid wrap-around artifact from maternal anatomy. Consequently, achieving clinically useful spatial and temporal resolution while maintaining a reasonable scan time is difficult with the conventional sequences available on most scanners.

Managing the length of fetal MRI acquisitions is particularly important given the periodic motions (fetal respiratory movements, fetal cardiac motion, maternal respiration) and stochastic motions (gross fetal movement) that can degrade image quality.

In pediatric and adult patients, a combination of cardiac gating and breath-holding or respiratory navigation is used to maintain diagnostically useful image quality. Unfortunately, a fetal electrocardiogram (ECG) signal is not readily available in the MRI environment and maternal breath-holds are brief and ideally avoided to optimize maternal comfort.

As a result, standard methods for dynamic imaging of the heart are not directly translatable to fetal subjects. Considering these limitations, early feasibility of fetal cardiac MRI was demonstrated in animals,8–12 while human studies focused on fast 2D acquisitions as described in the following section.

STATIC IMAGING
Several groups have reported the use of single-shot balanced steady-state free precession (bSSFP) and fast spin echo sequences (HASTE, SS-FSE) to evaluate fetal cardiovascular anatomy and identify abnormalities.13–20 These sequences are attractive because they provide relatively high resolution (∼1.0 to 1.5 mm in-plane) static 2D images in short acquisition times ([greater, similar]500 ms), allowing for multislice (ie, multiplanar) protocols.

Although the temporal resolution of these early methods was too low to resolve fetal cardiac motion, resulting in anatomical blur of dynamic structures, static MRI remains useful for identifying gross anatomy and unusual extracardiac abnormalities that may affect the diagnosis of cardiovascular malformations, such as persistent left superior vena cava or inferior vena caval interruption.21

These strengths become more apparent in late gestation when greater fetal size facilitates static MRI, and when echocardiography is more challenging. For reference, Fig. ​Fig.11 shows example SSFP and SS-FSE images of the fetal heart highlighting both bright-blood and black-blood strategies, respectively, which can be used to assess the fetal cardiac anatomy.

In addition to the structural information provided by these sequences, the repeated acquisition of bSSFP images in the same anatomical location over time has been used to provide a dynamic “real-time” assessment of the fetal heart including measurements of cardiac function.13,15,17,22–24

However, the spatiotemporal resolution of such real-time methods has historically been inadequate to resolve valvular functionality and to visualize the end-systolic phases of the fetal cardiac cycle, leading groups to focus instead on methods for CINE imaging.

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FIGURE 1
Static balanced steady-state free precession (bSSFP) bright-blood image (left) and single-shot fast spin-echo (ss-FSE) black-blood image (right) in a 38-week fetus with a right ventricular mass (arrowed). Reprinted with permission from Prenat Diagn 2016; 36:916–925 used under CC BY. Caption adapted from the original. Right (R) and left (L) heart sides are labelled.

CINE IMAGING
Time-resolved (CINE) bSSFP acquisitions are an integral facet of postnatal cardiac MRI examinations providing assessment of both cardiac structure and function. Using readily available sequences, high spatial and high temporal resolution images (∼1 × 1 mm2, <50 ms) may be acquired by synchronizing the sequence to the patient’s heart rate using an ECG signal (cardiac gating).

Unfortunately, a fetal ECG signal is not available in the MRI environment precluding conventional CINE imaging of the fetal heart. Nevertheless, much work has been done to develop fetal CINE imaging using novel post-processing methods and external hardware devices for retrospective fetal cardiac gating.

FETAL CARDIAC GATING
Metric Optimized Gating
Metric optimized gating (MOG) extracts the fetal heart rate by iteratively reconstructing CINE images using a parameterized model of the cardiac cycle and then outputs the optimum image quality according to the minimized image entropy through time,25 space,26,27 or both.28

While this method was first developed for time-resolved phase-contrast measurements of fetal blood flow,25 it has since been applied to both Cartesian and radial bSSFP acquisitions and was the first method to demonstrate dynamic CINE MRI of the human fetal heart.26

By independently parameterizing each fetal cardiac trigger, this model accounts for beat-to-beat fluctuations in fetal heart rate for subsequent CINE reconstruction. For Cartesian data without acceleration, the computational time needed for MOG is minor (eg, <5 minutes per slice using conventional desktop computing); however, for acquisitions with more complex reconstructions (ie, compressed sensing), the increased computational demand has led groups to explore alternative fetal gating methods based on intermediate real-time reconstructions, including an alternative formulation of MOG as described by the next section.

Self-gating
Self-gating refers to strategies that extract periodic gating signals from the MRI data itself. These signals can then be used to retrospectively sort the data into high-quality gated images.29 Implementations of self-gating have used various k-space trajectories for data acquisition, including Cartesian, radial, and spiral trajectories, and also various metrics to detect the cardiac or respiratory cycles, including signal intensity modulation, center-of-mass tracking, and image correlation.30 In the context of fetal MRI, self-gating has been used to extract the heart-rate from radial data using a principal component-based filtering of the repeatedly sampled k-space center.31

Alternatively, self-gating signals have been extracted from intermediate real-time reconstructions of radial data by measuring the correlation between frames32 or applying MOG to the real-time images, with compressed sensing reconstruction of each real-time image series requiring approximately 120 minutes per slice using conventional desktop computing.33

Potential challenges of non-Cartesian sampling include nonuniform clustering of data after temporal sorting, k-space trajectory errors, and off-resonance artifact (these latter issues being fairly benign for in utero radial imaging at 1.5T).34,35 In addition, fetal heart rates have been estimated directly from the temporal frequency spectrum of Cartesian real-time images, that is, the temporal Fourier transform of the image series, as the periodicity of the beating fetal heart appears as a local maximum in the spectrum within the range of expected heart rates.36

Hardware
Dramatic advances in fetal cardiovascular MRI have been demonstrated using the tailored acquisition and reconstruction methods described above. These methods, however, have limitations including relatively long reconstruction times that currently prevent evaluation of images during the MRI examination.

To address these limitations, researchers are developing novel external hardware to monitor the fetal cardiac cycle during MRI data acquisition. The most mature device for this purpose uses an MR-compatible Doppler Ultrasound Gating (DUS) probe placed over the maternal abdomen.37,38

This nonimaging device monitors motions associated with the fetal cardiac cycle, such as blood flow and cardiac contraction, based on a Doppler waveform. Triggers derived from this waveform are supplied to the MRI scanner to synchronize data acquisition. A practical benefit of this approach is the ability to use established cardiovascular protocols for fetal imaging, which provide immediate in-line image reconstructions to support clinical work-flow.39

Such devices may also facilitate studies that require prospective triggering, for example, in applications such as triggered T1 or T2 mapping.40 Drawbacks to this approach, as with any external device, include patient preparation time and equipment procurement. Furthermore, monitoring the fetal position to ensure it lays within the detection range will likely require pairing such devices with appropriate acquisition schemes, resulting in more elaborate and slower reconstructions.

VOLUMETRIC RECONSTRUCTION
The majority of fetal cardiac MRI is done using fast 2D acquisitions to minimize the impact of fetal and maternal motion. However, the underlying fetal anatomy is 3-dimensional and would be best represented as volumetric data to aid interpretation and assessment. Unfortunately, 3D MR data sets require several seconds to acquire and, consequently, are likely to be corrupted by motion and cardiac pulsation. An inventive solution to this problem is to use a multiplanar acquisition and combine the 2D images using volumetric reconstruction methods.

Volumetric reconstruction of 2D fetal MRI was first demonstrated for fetal brain imaging43–46 and subsequently applied to the fetal body47 as well as the placenta.48 These techniques use scattered data interpolation to achieve volumetric reconstructions from multiplanar 2D SS-FSE MR images.

Initial implementations interleaved interpolation with motion correction to generate 3D data, using either cubic B-spline45 or Gaussian kernel-based46 interpolation. Subsequently, an error minimization (super-resolution) approach was introduced to reduce the blurring effect from thick-slice MR images when using Gaussian kernel-based interpolation43 and outlier rejection was employed to reduce the impact of voxels corrupted by motion and images misaligned to the volume,43,44 removing the need for manual exclusion of inconsistent data. Signal intensity-matching was also added to increase data consistency leading to improved volumetric reconstructions.44,49

Methods for volumetric reconstruction of the fetal heart have now been developed for both static (3D) visualization of the fetal heart and extracardiac vasculature50 as well as CINE (4D) whole-heart visualization.42 Volumetric reconstruction from 2D MRI has several characteristics that are advantageous for fetal cardiac imaging.

First, the acquisition of multiplanar 2D MRI for volumetric reconstruction is robust to motion and does not require highly specific scan plane prescriptions to capture the desired anatomical features, which can be a challenge in 2D single-slice MRI. Second, both in-plane and through-plane motion can be corrected. Lastly, the reconstructed data can provide full coverage of the entire fetal heart, allowing for comprehensive assessment of fetal cardiovascular anatomy.

Figure ​Figure44 shows an example of the motion-corrected 3D volumetric reconstruction framework, originally used for fetal brain MRI,44 adapted to T2-weighted SS-FSE MR images of the fetal heart. Blood flowing through the cardiovascular system has a hypointense signal in the SS-FSE images and the extracardiac vasculature is well defined.

Such 3D reconstructions allow for detailed depiction of cardiovascular anatomy, particularly the aortic arch and pulmonary vessels, with improved diagnostic quality compared with uncorrected 2D SS-FSE.50 However, due to the signal characteristics of SS-FSE and the long acquisition time relative to the cardiac cycle (∼500 to 1000 ms), the heart and the roots of the great vessels appear as a nearly homogeneous signal region with little definition of intracardiac features in both the acquired 2D images and, consequently, the static 3D reconstruction.

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FIGURE 4
Volumetric reconstruction of T2-weighted multiplanar single shot fast spin echo (ss-FSE) MRI in a 33-week gestational age fetus with coarctation of the aorta. A volume rendering of the blood pool is shown in posterior projection (top left) and left lateral projection (top right). The bottom panel shows planes from the volumetric reconstructed data in transverse (Tra), coronal (Cor), and sagittal (Sag) orientations. The aorta (Ao), arterial duct (AD), descending aorta (DAo), aortic isthmus (i), pulmonary artery (PA), transverse arch (TA), and superior vena cava (SVC) are labeled. Reprinted with permission from Lancet 2019; 393:1619–1627 used under CC BY.

Figure ​Figure55 shows an example 4D reconstruction of a healthy fetal heart, acquired using real-time bSSFP instead of SS-FSE, showing the great vessels as well as intracardiac anatomy. These data could be resliced in any 2D plane or cardiac phase, allowing for optimal anatomical views and facilitating understanding of the spatial relationships of cardiovascular structures. This 4D reconstruction framework42 combines the motion-tolerant, image-domain 2D fetal cardiac CINE technique36 with a 3D volumetric reconstruction technique,44 and adds a temporal component to the volumetric reconstruction to generate dynamic volumes.

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FIGURE 5
4D CINE volumetric reconstruction of the heart of a healthy 28-week gestational age fetus from multi-planar real-time balanced steady-state free precession (bSSFP) MRI. (A) Volume rendering of blood pool in diastole showing arrangement and connections of chambers and vessels, for reference. The reconstructed 4D data are shown resliced in (B) 4-chamber, (C) mid-short axis, (E) right ventricular outflow tract, (F) left ventricular outflow tract, (G) aortic arch, and (H) 3-vessel views. (D) A line profile at the intersection of the 4-chamber and mid-short axis views (dashed yellow lines) shows the contraction and dilation of the ventricles with cardiac phase (An external file that holds a picture, illustration, etc.
Object name is rmr-28-235-i001.jpg). Ventriculoarterial connections can be seen in outflow tract views with the pulmonary artery (PA) from the right ventricle (RV) in (E) and the aorta (Ao) arising from the left ventricle (LV) in (F). Systemic venous connections of the superior (SVC) and inferior (IVC) vena cava with the right atrium (RA) can also be seen in (F). The ductal arch (DA) can be seen in both (E) and (H), connecting the PA to the descending aorta (DAo), while the Ao arch can be seen in (G) and (H). All boxes bounding the resliced views measure 65 × 65 mm. The fetal heart is shown in radiological orientation, that is, image axes up and right relative to the page correspond to left, anterior, and/or superior anatomical directions. Views are shown using spatial B-spline interpolation to avoid voxel distortion. Reprinted with permission from Magn Reson Med 2019; 82:1055–1072 used under CC BY.

reference link : https://europepmc.org/article/pmc/pmc6791520


Journal information: Nature Communications

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