As generally known, it proved to be particularly helpful to prepare the children and their parents/caregivers in advance for the upcoming MP-MRI examination.

The following protocol for the MRI examinations has been implemented: (i) distribution of child-friendly information material including imitation of MRI measurement at home (Figure 3 and Table 1), (ii) invitation to an intro-visit at the MRI, (iii) age-appropriate, playful introduction to the MRI device on-site (e.g., fairy tale about resident little magnet wizards, practical experiment using a tennis ball filled with nails etc.), (iv) opportunity to listen to self-chosen audio plays or music during the scan, (v) parents can stay in the scanner cabin and (vi) close motivational-supportive conversation with the child during the examination via intercom. With this approach, we achieved a feasibility rate of 96% from 5 years age onwards (number of completed scanning protocol and diagnostic image quality suitable for post-processing divided by number of attempted scans, shown in a prospective, observational study) (21). Of 52 children aged between 5 and 7 years, 50 children completed the full scanning protocol, one child refused lying in the scanner and another child stopped the examination after one acceptable functional scan resulting in an uncompleted morphological scan. The most decisive factor for good feasibility was age as in children aged between 3 and 4.9 years only 10 of 30 individuals agreed on lying in the scan device (feasibility rate 33%). However, these 10 patients, willing to start the examination, completed it successfully (21).

In the following medical consultations, both patients and physicians profit from the MP-MRI color-coded and defect maps, visualizing affected regions and extent of ventilation and perfusion impairment.

In our center, MP-MRI measurements are performed on a clinical whole-body Siemens 1.5 T scanner (applicability on scanners of other manufacturers and corresponding adaptation of the sequences is currently in progress). A close collaboration between Pediatric Pulmonology and Pediatric Radiology as well as fixed time slots per week facilitate applicability. We apply functional alongside structural sequences to ensure a comprehensive imaging of the lung, with MP-MRI accounting for 7.9 + −1.8 min of the average examination time of 25.1 + −4.6 min (21). To avoid longer investigations than usual, we limited the structural sequences to the most relevant ones (details presented in the OLS). As no sedation or specific breathing maneuvers are required, the additional effort for staff in charge is minimal. MP-MRI sequences are done at the end and as such, only measurement zones need to be defined.

The analysis of the MP-MRI scan data obtained and the computation of outcome values is currently carried out using a pipeline In our center, this is sustained by specialized biomedical engineer. But as the current version of the processing pipeline is available as a docker container, there is no strict qualification requirement. The software can be also installed and maintained by an IT person with knowledge of a Linux operating system on an intermediate level. However, the software is still in a translational phase and is not a commercially certified product. Thus, there is no dedicated official support for it.

We have successfully automated each step for reproducible application in research and clinics. The total calculation time required is 20 min per subject (22). Regarding eventual motions of the young patients during the MRI examination, the amplitude of motion is detected during the image registration process. Images with a motion amplitude higher than a threshold will be discarded in the further analysis. However, as with every MRI examination, a severe bulk motion during the scan will result with inferior or undiagnostic image quality. Further, we implemented a validated artificial neural network to automatically segment the lung areas on the MRI images (23) and the subsequent analysis are conceptually designed to be robust to minor segmentation inaccuracies (22). Further, we replaced time-consuming visual scoring of defect maps (24) by quantifiable and automatically calculable outcome values: (i) relative lung volume with impaired ventilation or perfusion (VDP, QDP) (21, 23, 25–31), (ii) relative lung volume with combined ventilation and perfusion defect (VQD_match) (30) and (iii) defect homogeneity (defect distribution index: DDI) (32). The latter numerically quantifies how clustered or scattered the impaired lung regions are which would otherwise have to be recognized visually by the human observer (32). Finally, an automatically generated pdf report includes color-coded maps in addition to numerical values (Supplementary Figure S2).

Additionally, we constantly incorporate the user feedback from clinicians, radiologists and research group members in close cooperation with computer scientists and physicists involved. When investigating innovative ideas and implementing updates, the immense number of measurements conducted and the great variety of case studies available have proven to be central to success.

We report here the positive experiences with the implementation of MP-MRI measurements in our department. Especially the non-invasiveness of the examination contributes to the acceptance of the examination in healthy children within study protocols. The children quickly lose their fear of the MRI device if they are gently introduced to it in advance. As MP-MRI is done within few minutes, adding the sequences to structural sequences does not change overall scan time substantially. The most challenging point in our institution was the installation of the sequences on the different MRI devices along with training of staff and connecting the data analysis pipeline for an automated workflow with the clinical information system, as the NCE-MRI techniques are not FDA-approved. However, the achieved unique collection of follow-up measurements and case studies has been a great resource for configuring reliable updates and exploring innovative ideas.

This is a 14-year-old male patient with CF before the approval of triple cystic fibrosis transmembrane conductance regulator (CFTR)-modulator therapy. He showed clinical deterioration and lung function decline over the last months. We performed an MP-MRI scan (Figure 4) in addition to structural MRI. The pronounced impairment of ventilation and perfusion in the right upper lung shown in MPI-MRI was together with the morphological images suggestive of mucus plugging of the right upper lobar bronchus. After bronchoscopic removal of the large mucus plug, symptoms resolved. Lung function improved and a follow-up MP-MRI revealed improvement of lung ventilation and perfusion at the right upper lobe. A sustained recovery of lung function was achieved later through introduction of CFTR modulator therapy.

To conclude: MP-MRI helped to identify and quantify the region of poorly ventilated and/or perfused areas, that potentially were responsive to bronchoscopic intervention.

In a 5-year-old boy, necrotizing pneumonia of the right lung resulted in surgical removal of the right upper lobe. A prolonged course of disease with significant respiratory limitations and persistent oxygen requirement followed. A computed tomography (CT) scan (not shown) revealed marked dystelectatic and scarring changes of the remaining right lung. To address the discussion whether this specific part of the lung was still functional (thus ventilated and perfused) or should also be removed in order to reduce the risk of further infections, we performed an MP-MRI measurement (Figure 5). The scan showed impaired, but existing perfusion and adequate ventilation of the remaining lung indicating residual function. Consequently, the resection was waived. In the further course, the patient improved clinically with improvement of lung function. A follow-up MP-MRI two and four years later showed normal ventilation and only slightly impaired perfusion in the lung area affected.

To conclude: MP-MRI allowed to specifically examine the post-infectious function of a lung lobe and helped in the discussion of indication for surgical intervention.

A 16-year-old male adolescent with sickle-cell disease (SCD) suffered from recurrent episodes of acute chest syndrome. Lung function showed a mixed ventilatory impairment with airway obstruction, reduced functional vital capacity and increased ventilation inhomogeneity. For a better understanding of the underlying pathophysiological aspects, we performed an MP-MRI scan (Figure 6). We found normal ventilation but patchy-dispersed perfusion impairment, consistent with the vaso-occlusive nature of sickle cells.

To conclude: MP-MRI helped to visualize the pathophysiological nature of lung impairment, i.e., vasoocclusive processes, and to rule out other potential causes of lung pathology in this patient with SCD.

This is a 14-year-old male patient with post-infectious bronchiolitis obliterans. Diagnostic tests showed fixed airway obstruction and hyperinflation, regular ventilation inhomogeneity and typical radiological findings in CT scans (mosaic perfusion, bronchiectasis of the right upper and lower lung lobes; images not shown). Using MP-MRI (Figure 7), we were able to link the information from global lung function derived from pulmonary function tests with spatially resolved functional impairment provided by the MP-MRI scans, illustrating that ventilation and perfusion were both impaired to a higher degree in the right lung compared to the left side.

To conclude: MP-MRI helps not only to characterize better the regional impairment of lung function in addition to global lung function tests measured at the mouth. In this patient with post-infectious bronchiolitis obliterans it helped to quantify functional impairment due to bronchiectasis and ventilation inhomogeneity and visualize this regional functional deficit for better understanding of the disease process.

A 9-year-old girl with a large left-sided congenital diaphragmatic hernia (prenatal diagnosis and installation of an intratracheal plug, postnatal repair of the diaphragmatic hernia using a muscle flap) suffered from exercise-dependent respiratory symptoms. Lung function tests showed reduced vital capacity, hyperinflation and ventilation inhomogeneity. MP-MRI showed significantly decreased perfusion of the left lung combined with reduced ventilation (Figure 8). This clear picture was confirmed by the morphological MRI, where a rarification of the vessels was seen (panel a, Figure 8). This suggests altered fetal lung development and/or dysproportional catch-up growth [further results published in (30)].

To conclude: MP-MRI enables to examine and visualize the function of the left and right lung separately in patients with side-related anatomic aberrations.

In the clinical setting, different disease entities exist, in which patients, parents and care givers benefit from the opportunity to assess ventilation and perfusion of the lung in a spatially resolved manner and visualize any impairment. This helps in clinical decision-making regarding possible therapies, allows targeted follow-up of affected lung regions and helps to more specifically understand and explain the underlying lung physiology. The easy applicability and the non-invasiveness of MP-MRI examinations are additional factors in favor of their use.