Ultrashort echo time MRI of the lung in children and adolescents: comparison with non-enhanced computed tomography and standard post-contrast T1w MRI sequences

Magnetic resonance imaging (MRI) of the lung is increasingly established in children and adolescents [1‐7]. According to the recently published systematic review of Hirsch et al. [2], lung MRI enables to replace up to 90% of paediatric chest computed tomography (CT) examinations. In contrast to adults, paediatric primary lung tumours are rare with the majority of pulmonary malignancies being of metastatic origin [2, 4, 8, 9]. However, the detection of subtle pulmonary pathologies, particularly tiny nodules, by lung MRI is still challenging [10‐13]. Sub-centimetre sized pulmonary nodules are mostly benign in general paediatric populations [14‐16]. Otherwise, even small pulmonary nodules can be malignant in children with proven malignancies, as many paediatric tumours can develop metastases in the lungs [4, 17].

Because children are more sensitive to negative effects of X-ray exposure than adults, one main benefit of lung MRI is the absence of any radiation exposure [2‐5]. Further advantages are the possibility to visualise pathologies by using differently weighted sequences and to provide morphologic as well as functional information [2‐5, 18, 19]. The main issues of lung MRI are low proton density of lung parenchyma and strong magnetic susceptibility effects resulting in short T2 and T2* relaxation times [10, 18‐22]. Further challenges are motion artefacts due to patient movement, cardiac pulsations or respiration, which are particularly problematic for younger children who have high cardiac pulse and respiratory rates as well as low capabilities to cooperate during breath-hold manoeuvres [2, 4, 23]. T2-weighted lung MRI sequences can be acquired by breath-hold manoeuvres and/ or by respiratory navigator gating; this respiratory navigator gating technique cannot be sufficiently used in T1-weighted sequences due to their short echo (TE) and repetition times (TR) [18, 19].

Standard T1-weighted lung  MRI sequences, currently mainly used in clinical routine, are acquired during breath-hold technique with common slice thicknesses of ≥ 2.5 mm [18, 24, 25]. The recently developed ultrashort echo time (UTE) sequences have very short TE on the order of < 0.1 ms combined with rapid acquisition due to short TR, which makes them suitable to acquire signals from tissues with short T2/T2* relaxation times [18, 26‐29]. Three-dimensional (3D) UTE techniques allow isotropic resolutions with slice thicknesses around 1 mm and, due to their numerous excitations, can be acquired during free-breathing of the patients [26‐31]. As far as we know, this is the first study, which has performed a detailed analysis of a 3D UTE sequence of the lung with isotropic voxels in a paediatric oncologic population, including an objective and subjective imaging assessment. The aim of this prospective study was to compare the UTE technique to chest CT, which is still the gold standard, and to two T1-weighted breath-hold sequences (2D incoherent and 3D volume interpolated gradient echo (GRE)), which are currently the most performed standard T1-weighted sequences in clinical routine. The focus of this investigation was set on the diagnosis of challenging, subtle, pulmonary pathologies, including small nodules and ground-glass opacities.

Thin-section UTE imaging is a sensitive technique to detect pulmonary nodules and parenchymal areal opacities in children and adolescents with malignancies. To our knowledge, this is the first study, which compared the UTE sequence with two T1-weighted standard sequences, mostly performed in clinical routine, and to the still gold standard chest CT in a paediatric oncologic population. The image quality parameters of the UTE sequence are higher compared to both GRE sequences, except for the contrast.

The high contrast of the incoherent GRE sequence is a direct consequence of the scan parameters, resulting in high signal even from tissues with longer T1-relaxation times. The ultrashort echo time of the UTE sequence leads to substantial signal gain in the lung parenchyma [27, 42]. Nevertheless, despite this reduction of contrast, which could be mitigated by increasing the TR (albeit at the cost of scan time), the nodular detection rate of UTE was superior compared to the other two MRI sequences, mainly due to the reduced artefacts and the improved lesion sharpness (due to the high isotropic resolution). The mean overall image quality of 4.1 for the UTE sequence in our study is comparable with published findings in adults. Ohno et al. [43] reported a mean overall image quality of 4.4 with 1 mm³ isotropic UTE imaging, using a similar visual 5-point Likert scale. In the study of Cha et al. [36], the UTE sequence resulted in a mean overall image quality of 3.9–4.0 and a mean value of 3.7 for the presence of image artefacts, scored by two readers with a similar 5-point Likert scale.

The significantly higher detection of pulmonary nodules with UTE sequence in our study is also similar to published reports in adults, which compared MRI sequences to chest CT. In the study of Burris et al. [12], the overall detection rate was 73% (60 of 82 nodules) for UTE and 30% (25 of 82 nodules) for dual-echo GRE sequences, whereby the nodules had a mean short-axis diameter of 6.2 mm. Wielpütz et al. [39] reported a detection rate of the UTE sequence of 92.5% for nodules with a relatively high mean maximum long-axis diameter of 17.4 mm. In our investigation, the UTE sequence was most beneficial, compared to GRE images, in diagnosing challenging nodules with sizes up to 4 mm. In the study of Burris et al. [12], the higher detection of the UTE sequence was statistically significant for nodules with diameters ≥ 4 mm, but not for sizes ≥ 8 mm. We detected significantly more solid and subsolid nodules with the UTE sequence compared to the GRE images. Ohno et al. [44] evaluated in adults the performance of UTE imaging compared to chest CT depending on the nodular appearance and found that 35.3% ground-glass, 33.3% partly solid, and 94.7% solid nodules (long-axis diameters of 4–6 mm) were detected with the UTE technique in consensus reading. The UTE sequence is also suited in diagnosing subsolid nodules, which are diagnostically challenging. This higher detection in our study is most likely due to the combination of higher spatial resolution and higher lung signal of the UTE technique. However, the UTE sequence showed no significant benefit in detecting calcified nodules in our study. Calcified nodules remain a diagnostic challenge for MRI due to their low signal intensity [4, 17, 45]. Although most calcified pulmonary nodules are likely to be benign, some bone-forming paediatric tumours, e.g., osteosarcomas, can show metastases with at least some calcifications in the lungs [4, 17, 45].

As described, the UTE sequence missed no patients with pulmonary nodules; out of the 4 CT examinations with solely 1 nodule, the UTE technique detected all of the 4 nodules in the initial reading. Thus, the missing of some nodules by UTE did not have a significant impact on the treatment of the patients. Furthermore, 7 of the 15 in total missed nodules could be visualised on MRI by considering all sequences (with also T2-weighted images). Although the radiation doses of chest CT examinations are quite low by using new technologies, any radiation exposure should be avoided in children if radiation-sensitive organs, e.g., thyroid gland, breasts, red bone marrow, are located in the exposure fields and in the case of tumour predisposition syndromes [2]. The application of contrast media may be favourable for diagnosing mediastinal and bihilar lymph node metastases on MR and CT imaging, whereas enhanced CT examinations result in higher radiation exposures than unenhanced CT imaging. Another advantage of MRI is the distinct diagnosis of bone metastases [3, 5, 45]. As no breath-hold manoeuvres are necessary for the performance of the UTE sequence, the higher detection rates and the possible acquisition without intubation anaesthesia compensate for the higher acquisition time of the UTE sequence compared to the common standard T1-weighted GRE sequences.

Lung MRI is increasingly performed in children for diagnosing pulmonary infections [46, 47]. All consolidations were detected with all three MRI sequences in our study, in contrast to the more subtle ground-glass opacities and parenchymal bands. Due to the low number of these pathologies, the higher detection rate with UTE compared to the GRE images was statistically not significant. The diagnostic challenge of detecting ground-glass opacities by MRI has been reported. Sodhi et al. [46] evaluated an MRI protocol with T2-weighted and volume interpolated GRE sequences and found a high correlation with chest CT for the diagnosis of consolidations, but not for ground-glass opacities in children (age range 5–15 years). Roach et al. [48] compared UTE imaging (acquisition time 5–10 min) with chest CT in patients with early cystic fibrosis lung disease (mean age 31.8 months) and reported Pearson correlation coefficients of 0.45 for diagnosing consolidations and of 0.21 for diagnosing ground-glass opacities. In older patients with cystic fibrosis (mean age 22.6 years), Dournes et al. [49] found that their evaluated UTE sequence showed good to very good agreement with CT regarding all morphologic pulmonary manifestations, such as bronchiectasis, peribronchial thickening, and mosaic pattern. Thus, the UTE technique becomes increasingly important for the diagnosis of subtle parenchymal pathologies.

Since the inclusion criteria required a homogeneous study design, only a limited number of patients could be included in this prospective study. All patients had clinical indications for the administration of MR contrast media; no agent was applied only for the study purpose. The use of contrast medium might have had an impact on the diagnostic performance, as the detection of pulmonary nodules can be improved by possible enhancement [10, 40]. However, MR contrast media must be in general administered judiciously in children and adolescents, due to possible gadolinium deposition in different tissues, such as brain, bone, or liver, and the brain development during childhood and adolescence [50]. The evaluated sequences were acquired at the end of the MRI examinations; thus, image artefacts due to patient movements or less deep anaesthesia may have occurred. Furthermore, a wash-out of the contrast media might have developed. The diagnostic performance of the T1-weighted sequences, particularly the UTE technique, which was performed as the last sequence, could be even higher if they were acquired earlier in the MRI examinations.

In conclusion, the findings of our study indicate that UTE imaging of the lung leads to improved diagnostic performance compared to conventional T1-weighted sequences in children and adolescents, if chest CT served as the gold standard. In particular, the detection rate of small pulmonary nodules ≤ 4 mm is superior with UTE imaging, presumably due to the higher spatial resolution and reduced artefacts. The visibility of subtle, diffuse parenchymal lesions, e.g., ground-glass opacities, in UTE images is promising. Lung MRI may be used instead of chest CT examinations during the staging of children with oncologic diseases, particularly if the diagnosis of lymph node and bone metastases are also important issues.