Elexacaftor/tezacaftor/ivacaftor improves chronic rhinosinusitis detected by magnetic resonance imaging in children with cystic fibrosis on long-term therapy with lumacaftor/ivacaftor.

INTRODUCTION: Previous studies using magnetic resonance imaging (MRI) demonstrated early onset and progression of chronic rhinosinusitis (CRS) from infancy to school age, and response to lumacaftor/ivacaftor (LUM/IVA) therapy in children with cystic fibrosis (CF). However, the effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CRS detected by MRI in children with CF and at least one F508del mutation, and potential incremental effects of ELX/TEZ/IVA compared to LUM/IVA in F508del homozygous children have not been studied. METHODS: 30 children with CF with at least one F508del mutation underwent three longitudinal paranasal sinus MRI before (MRI1), without (n = 16) or with LUM/IVA therapy (n = 14, MRI2), and with ELX/TEZ/IVA therapy (MRI3, mean age at therapy initiation 11.1 ± 3.4y, range 6-16y). MRI were evaluated using the CRS-MRI score. RESULTS: After therapy initiation with ELX/TEZ/IVA, the prevalence and in maxillary and sphenoid sinuses the dominance of mucopyoceles decreased (35% vs. 0 %, p<0.001 and 26% vs. 8 %, p < 0.05, respectively). This leads to a reduction in mucopyocele subscore (-3.4 ± 1.9, p < 0.001), and sinus subscores in MRI3 (maxillary sinus: -5.3 ± 3.1, p < 0.001, frontal sinus: -1.0 ± 1.9, p < 0.01, sphenoid subscore: -2.8 ± 3.5, p < 0.001, ethmoid sinus: -1.7 ± 1.9, p < 0.001). The CRS-MRI sum score decreased after therapy initiation with ELX/TEZ/IVA by -9.6 ± 5.5 score points (p < 0.001). The strength in reduction of mucopyoceles subscore and CRS-MRI sum score was independent of a pretreatment with LUM/IVA from MRI1-MRI2 (p = 0.275-0.999). CONCLUSIONS: ELX/TEZ/IVA therapy leads to improvement of CRS in eligible children with CF. Our data support the role of MRI for comprehensive monitoring of CRS disease severity and response to therapy in children with CF.

Magnetic Resonance Imaging of Pulmonary and Paranasal Sinus Abnormalities in Children with Primary Ciliary Dyskinesia Compared to Children with Cystic Fibrosis.

Rationale: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are characterized by inherited impaired mucociliary clearance leading to chronic progressive lung disease as well as chronic rhinosinusitis (CRS). The diseases share morphological and functional commonalities on magnetic resonance imaging (MRI) of the lungs and paranasal sinuses, but comparative MRI studies are lacking. Objectives: To determine whether PCD shows different associations of pulmonary and paranasal sinus abnormalities on MRI and lung function test results in children (infants to adolescents) compared with children with CF. Methods: Eighteen children with PCD (median age, 9.5 [IQR, 3.4-12.7] yr; range, 0-18 yr) and 36 age-matched CF transmembrane conductance regulator modulator-naive children with CF (median age, 9.4 [3.4-13.2] yr; range, 0-18 yr) underwent same-session chest and paranasal sinus MRI as well as spirometry (to determine forced expiratory volume in 1 s percent predicted) and multiple-breath washout (to determine lung clearance index z-score). Pulmonary and paranasal sinus abnormalities were assessed using previously validated chest MRI and CRS-MRI scoring systems. Results: Mean chest MRI global score was similar in children with PCD and CF (15.0 [13.5-20.8] vs. 15.0 [9.0-15.0]; P = 0.601). Consolidations were more prevalent and severe in children with PCD (56% vs. 25% and 1.0 [0.0-2.8] vs. 0.0 [0.0-0.3], respectively; P < 0.05). The chest MRI global score correlated moderately with forced expiratory volume in 1 second percent predicted in children with PCD and children with CF (r = -0.523 and -0.687; P < 0.01) and with lung clearance index in children with CF (r = 0.650; P < 0.001) but not in PCD (r = 0.353; P = 0.196). CRS-MRI sum score and mucopyocele subscore were lower in children with PCD than in children with CF (27.5 [26.3-32.0] vs. 37.0 [37.8-40.0] and 2.0 [0.0-2.0] vs. 7.5 [4.8-9.0], respectively; P < 0.01). CRS-MRI sum score did not correlate with chest MRI score in PCD (r = 0.075-0.157; P = 0.557-0.788) but correlated moderately with MRI morphology score in CF (r = 0.437; P < 0.01). Conclusions: MRI detects differences in lung and paranasal sinus abnormalities between children with PCD and those with CF. Lung disease does not correlate with CRS in PCD but correlates in CF.

Long-term effects of lumacaftor/ivacaftor on paranasal sinus abnormalities in children with cystic fibrosis detected with magnetic resonance imaging.

Introduction: Chronic rhinosinusitis (CRS) usually presents with nasal congestion, rhinorrhea and anosmia impacts quality of life in cystic fibrosis (CF). Especially mucopyoceles pathognomonic for CRS in CF may cause complications such as spread of infection. Previous studies using magnetic resonance imaging (MRI) demonstrated early onset and progression of CRS from infancy to school age in patients with CF, and mid-term improvements of CRS in preschool and school-age children with CF treated with lumacaftor/ivacaftor for at least 2 months. However, long-term data on treatment effects on paranasal sinus abnomalities in preschool and school-age children with CF are lacking. Methods: 39 children with CF homozygous for F508del (mean age at baseline MRI 5.9 ± 3.0 years, range 1-12 years) underwent MRI before (MRI1) and about 7 months after starting lumacaftor/ivacaftor and then annually (median 3 follow-up MRI, range 1-4) (MRI2-4). MRI were evaluated using the previously evaluated CRS-MRI score with excellent inter-reader agreement. For intraindividual analysis ANOVA mixed-effects analysis including Geisser-Greenhouse correction and Fisher's exact test, and for interindividual group analysis Mann-Whitney test were used. Results: The CRS-MRI sum score at baseline was similar in children starting lumacaftor/ivacaftor in school age and children starting therapy at preschool age (34.6 ± 5.2 vs.32.9 ± 7.8, p = 0.847). Mucopyoceles were the dominant abnormality in both, especially in maxillary sinus (65% and 55%, respectively). In children starting therapy in school age the CRS-MRI sum score decreased longitudinally from MRI1 to MRI2 (-2.1 ± 3.5, p < 0.05), MRI3 (-3.0 ± 3.7, p < 0.01) and MRI4 (-3.6 ± 4.7, p < 0.01), mainly due to a decrease in the mucopyoceles subscore (-1.0 ± 1.5, p = 0.059; -1.2 ± 2.0, p < 0.05; -1.6 ± 1.8, p < 0.01; and -2.6 ± 2.8, p = 0.417, respectively). In children starting lumacaftor/ivacaftor in preschool age, the CRS-MRI sum score remained stable under therapy over all three follow-up MRI (0.6 ± 3.3, p = 0.520; 2.4 ± 7.6, p = 0.994; 2.1 ± 10.5, p > 0.999 and -0.5 ± 0.5, p = 0.740; respectively). Conclusion: Longitudinal paranasal sinus MRI shows improvements in paranasal sinus abnormalities in children with CF starting lumacaftor/ivacaftor therapy at school age. Further, MRI detects a prevention of an increase in paranasal sinus abnormalities in children with CF starting lumacaftor/ivacaftor therapy at preschool age. Our data support the role of MRI for comprehensive non-invasive therapy and disease monitoring of paranasal sinus abnormalities in children with CF.

Longitudinal Magnetic Resonance Imaging Detects Onset and Progression of Chronic Rhinosinusitis from Infancy to School Age in Cystic Fibrosis.

Rationale: Chronic rhinosinusitis (CRS) contributes to morbidity in patients with cystic fibrosis (CF). However, longitudinal data on CRS onset and progression is lacking. Objectives: To longitudinally evaluate CRS in CF from infancy to school age with paranasal sinus magnetic resonance imaging (MRI). Methods: A total of 64 children with CF (mean age at baseline, 1.1 ± 1.6 yr; range, 0-5 yr) underwent a mean of 5.8 ± 2.2 (range, 3-11 yr) subsequent annual MRI examinations. Additional 24 children (9.2 ± 4.4 yr; range, 3-17 yr) homozygous for the F508del mutation underwent MRI before and at least 2 months after starting lumacaftor/ivacaftor. MRI was assessed using the previously evaluated CRS-MRI score. Results: In infancy, 65-87% of paranasal sinuses were opacified, and mucosal swelling was the dominant abnormality (58-97%). At preschool age (1-5 yr), 79-94% of sinuses were opacified (P < 0.05 vs. infancy), and mucosal swelling was the most dominant abnormality (79-94%; P < 0.05). At school age (at least 6 yr), almost all sinuses were opacified (71-99%; P < 0.001-0.357 vs. preschool age), and mucopyoceles were the dominant abnormality in maxillary and frontal sinuses (53-56%; P < 0.05-0.808). The CRS-MRI sum score increased from 22.4 ± 9.6 in infancy to 34.2 ± 9.6 in preschool age (P < 0.001) and was 34.0 ± 5.7 in school age (P = 0.052). In children under lumacaftor/ivacaftor therapy, the CRS-MRI sum score (-0.5 ± 3.3; P < 0.05) and maxillary sinus subscore (-0.5 ± 1.5; P < 0.05) improved. Conclusions: Longitudinal paranasal sinus MRI detects an early onset and progression of the severity of CRS from infancy to school age, and response to lumacaftor/ivacaftor therapy in children with CF. Our data support its role in the comprehensive noninvasive monitoring of CRS in children with CF. Clinical trial registered with www.clinicaltrials.gov (NCT02270476).

Magnetic resonance imaging detects improvements of pulmonary and paranasal sinus abnormalities in response to elexacaftor/tezacaftor/ivacaftor therapy in adults with cystic fibrosis.

BACKGROUND: Therapy with Elexacaftor/Tezacaftor/Ivacaftor (ETI) was recently approved for adult cystic fibrosis (CF) patients with at least one F508del mutation. However, its effects on structural and functional lung abnormalities and chronic rhinosinusitis have not been studied by imaging. METHODS: 19 adults with CF (mean age 31±9y, range 19-55y) underwent standardized chest magnetic resonance imaging (MRI), and nine also same-session sinonasal MRI, before (MRI1) and after (MRI2) at least one month (mean duration 5 ± 3mon) on ETI. 24 control CF patients (30±7y, range 20-44y) without ETI underwent longitudinal chest MRI, and eleven also sinonasal MRI, twice (mean interval 40±15mon). MRI was assessed using the validated chest MRI score and chronic rhinosinusitis (CRS)-MRI score. Forced expiratory volume in 1 s percent predicted (FEV1%) was measured in all patients. RESULTS: In controls, the chest MRI global score and CRS-MRI sum score were stable from MRI1 to MRI2. In patients under ETI, the chest MRI global score improved (-11.4 ± 4.6, P<0.001), mainly due to reduction of bronchiectasis/wall thickening and mucus plugging subscores (-3.3 ± 2.2 and -5.2 ± 1.5, P<0.001, respectively). The improvement in chest MRI score correlated well with improved FEV1% (r=-0.703, P<0.001). The CRS-MRI sum score also improved in patients under ETI (-6.9 ± 3.0, P<0.001), mainly due to a reduction of mucopyoceles in the maxillary and ethmoid sinus (-50% and -39%, P<0.05, respectively). CONCLUSIONS: MRI detects improvements of chest MRI and CRS-MRI scores in adult CF patients who first received ETI, demonstrating reversibility of structural lung and paranasal sinus abnormalities in patients with established disease.

3-T T2 mapping magnetic resonance imaging for biochemical assessment of normal and damaged glenoid cartilage: a prospective arthroscopy-controlled study.

This study evaluated the ability of T2 mapping to assess the glenoid cartilage using arthroscopy as the gold standard. Eighteen consecutive patients (mean age: 52.4 ± 14.72 years, including 12 men) with shoulder pain underwent T2 mapping at 3-T with subsequent shoulder arthroscopy. With correlation to cartilage-sensitive morphologic sequences regions-of-interest were placed in the corresponding T2 maps both in normal-appearing cartilage and focal cartilage lesions using a quadrant-wise approach. Inter-reader and intra-reader correlation coefficients (ICCs) between two independent radiologists as well as cut-off values with their sensitivities/specificities for the detection of cartilage damage were calculated. The mean T2 value for healthy cartilage was 23.0 ± 3 ms with significantly higher values in the superior quadrants compared to the inferior quadrants (p < 0.0001). In 5 patients with focal cartilage damage significantly higher T2 values of 44.7 ± 3.7 ms (P < 0.01) were observed. The maximum T2 value in normal cartilage (27.3 ms) was lower than the minimum value in damaged cartilage (40.8 ms) resulting in perfect sensitivities/specificities of 100% (95% confidence-interval 47.8-100.0) for all cut-off values between 27.3-40.8 ms. ICCs ranged between 0.63 and 0.99. In conclusion, T2 mapping can evaluate biochemical cartilage integrity and discriminates arthroscopy-proven healthy and damaged glenoid cartilage with high diagnostic performance.

[Radiologic diagnosis of pathologic fractures]. / Radiologische Diagnostik pathologischer Frakturen.

BACKGROUND: Pathologic fractures are fractures that occur without an adequate traumatic event due to focal benign or malignant skeletal lesions. The most common causes of pathologic fractures are cystic bone lesions, plasmocytoma or multiple myeloma, and the development of osseous metastases, which is increasing due to an aging general population and advances in cancer treatment. The differentiation of pathologic fractures from stress fractures, especially osteoporotic insufficiency fractures is crucial for correct treatment planning. OBJECTIVES: This review intends to explain the imaging characteristics of pathologic fractures. Moreover, it explains the role of imaging when pathologic fractures are suspected. In addition, the Mirels' score and the SINS (Spinal Instability Neoplastic Score), which are powerful yet easy-to-use tools for the assessment of the fracture risk of benign or malignant bony lesions of the extremities and the vertebral column, shall be introduced. MATERIALS AND METHODS: A PubMed literature search with the following terms was conducted: "pathologic fracture", "fatigue fracture", "insufficiency fracture", "treatment of pathologic fractures", "imaging of pathologic fractures", "fracture risk", "bone metastases", "MRI of pathologic fractures", "CT of pathologic fractures", "differentiation of pathologic and insufficiency fractures", "Mirels' score", "SINS" and "spinal instability neoplastic score". RESULTS: The definitions of pathologic, fatigue, and insufficiency fractures are explained. Moreover, the role of imaging in the clinical workup of suspected pathologic fractures and the differentiation of pathologic fractures from fatigue or insufficiency fractures as well as common scoring systems to assess the fracture risk of pathologic fractures are described.

MRI patterns indicate treatment success and tumor relapse following radiofrequency ablation of osteoblastoma.

Purpose: To explore the typical magnetic resonance imaging (MRI) pattern of osteoblastoma (OB) after radiofrequency ablation (RFA) treatment and to identify signs indicating treatment success or relapse.Materials and methods: Forty-four follow-up MRI examinations of 15 patients with OB who had undergone 19 RFA procedures were analyzed retrospectively. An early follow-up group (1-4 months after RFA) and a late follow-up group (8-131 months after RFA) were established. The groups were further subdivided according to treatment success. Images were analyzed for the presence of central nidus enhancement (CNE), peripheral nidus enhancement (PNE), perifocal bone marrow edema (PBME) and fatty nidus conversion (FNC).Results: The early follow-up MRI image from every patient in the treatment success group exhibited a target-like appearance with negative CNE and positive PNE or PBME. PNE and PBME were observed in 93% and 71% of the early follow-up images, respectively. A target-like appearance was observed in 25% of the late follow-up images, and PNE and PBME were each observed in 20% of these images. FNC was not observed in the early follow-up images, but was seen in 55% of the late follow-up images. All three MRI images of the patients exhibiting clinical recurrence demonstrated strong CNE, PNE and extensive PMBE, which was in contrast to the images of the patients exhibiting treatment success.Conclusion: A target-like appearance of OB in early follow-up MRI examination indicates treatment success. PNE and PBME typically reduce over time and can lead to FNC in successfully treated patients. CNE recurrence, PNE and extensive PBME are signs of relapse.

Magnetic Resonance Imaging Detects Chronic Rhinosinusitis in Infants and Preschool Children with Cystic Fibrosis.

Rationale: Chronic rhinosinusitis (CRS) contributes to disease burden of patients with cystic fibrosis (CF). However, its onset and progression in infants and preschool children with CF remain poorly understood.Objectives: To determine the prevalence and extent of CRS in young children with CF using magnetic resonance imaging (MRI).Methods: MRI was performed in sedation in 67 infants and preschool children with CF (mean age 2.3 ± 2.1 yr; range 0-6 yr) and 30 non-CF control subjects (3.5 ± 2.0 yr; range 0-6 yr). Paranasal sinus dimensions and structural abnormalities, including mucosal swelling; mucopyoceles; and nasal polyps of the maxillary, frontal, sphenoid, and ethmoid sinuses; and, in addition, medial maxillary sinus wall deformation, were assessed using a dedicated CRS MRI scoring system.Results: Pneumatization and dimensions of paranasal sinuses did not differ between the two groups. MRI detected an increased prevalence of mucosal swelling (83% vs. 17%; P < 0.001), mucopyoceles (75% vs. 2%; P < 0.001), polyps (26% vs. 7%; P < 0.001), and maxillary sinus wall deformation (68% vs. 2%; P < 0.001) in infants and preschool children with CF compared with age-matched control subjects. Furthermore, the extent of these abnormalities was also increased with a MRI sum score of 22.9 ± 10.9 in CF compared with 4.5 ± 7.6 in non-CF control subjects (P < 0.001).Conclusions: MRI detected normal dimensions of paranasal sinuses, and a high prevalence and severity of paranasal sinus abnormalities due to CRS in infants and preschool children with CF without radiation exposure. Our results support the development of MRI for sensitive noninvasive diagnosis and monitoring of CRS in young children with CF, and as outcome measures for clinical trials.Clinical trial registered with www.clinicaltrials.gov (NCT00760071).

Feasibility of using half-dose Gd-BOPTA for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at the knee, compared with standard-dose Gd-DTPA.

BACKGROUND: We sought to replace full-dose Gd-DTPA with safer and lower-dose contrast agents for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Gd-BOPTA has a lower intrinsic nephrogenic systemic fibrosis risk and a 2-fold higher relaxivity at 3T; thus, the contrast agent dose may be halved, further reducing contrast agent-dependent risks. PURPOSE: To compare the feasibility of using half-dose, high-relaxivity Gd-BOPTA vs. standard-dose Gd-DTPA for dGEMRIC. STUDY TYPE: Prospective observational study. SUBJECTS: Eleven healthy volunteers (five women, mean age 25.7 years) and 10 patients with knee pain (three women, mean age 36.7 years; nine with chondromalacia). FIELD STRENGTH/SEQUENCES: 3D T1 -weighted volumetric breath-hold examination (VIBE) sequence at 3T. ASSESSMENT: Knee dGEMRIC was performed twice, first using 0.1 mmol/kg Gd-BOPTA and 4 weeks later using 0.2 mmol/kg Gd-DTPA. Contrast penetration was studied using pre- and 60-120-min postcontrast imaging in volunteers and pre- and 90-min postcontrast imaging in patients. Femoral cartilage lesions were assessed using modified whole-organ MRI scores. Healthy cartilage and partial-thickness lesions were compared using region-of-interest analyses by independent readers. STATISTICAL TESTS: Linear mixed-effect-models, area under receiver-operating-characteristic curve (AUC) analysis, intraclass correlation (ICC). RESULTS: In healthy volunteers, Gd-BOPTA and Gd-DTPA T1 -values did not differ significantly at any timepoint (P = 0.164-0.995). In patients, Gd-BOPTA T1 -values (743.33 ± 72.015 msec) were higher than Gd-DTPA T1 -values (681.24 ± 67.635 msec, P = 0.030). Gd-BOPTA and Gd-DTPA detected chondromalacia areas equally well, with significantly lower T1 -values than in healthy cartilage (P < 0.001) and nonsignificantly different AUCs (0.92 and 0.96, P = 0.27). The absolute decrease in T1 -values between healthy and pathological cartilage was similar (Gd-BOPTA: 149.59 msec; Gd-DTPA: 149.44 msec, P = 0.99). ICCs were 0.83-0.98 for Gd-BOPTA and 0.80-0.98 for Gd-DTPA. DATA CONCLUSION: Gd-BOPTA might be used at half the Gd-DTPA dose in dGEMRIC, with similar contrast penetration and T1 -values in healthy cartilage and noninferior detection of cartilage damage. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:144-154.

Imaging of the Knee Following Repair of Focal Articular Cartilage Lesions.

Focal chondral or osteochondral lesions of the knee are common lesions involving either the cartilage layers or the cartilage layers and the subchondral bone. Despite their heterogeneous clinical presentation, they are important risk factors for the premature development of osteoarthritis. Therefore, early detection of osteochondral lesions and focal cartilage defects is crucial. In symptomatic (osteo-)chondral lesions, numerous therapeutic strategies, ranging from conservative treatment to surgical procedures such as marrow stimulation, osteochondral autograft transplantation, or autologous chondrocyte implantation are available. Musculoskeletal radiologists should be familiar with these surgical procedures, the evaluation of the postoperative findings as well as the possible complications when interpreting postoperative imaging studies. This review article describes the different surgical approaches to focal osteochondral lesions of the knee with emphasis on postoperative imaging findings and the pitfalls possibly encountered by the radiologist.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping of talar osteochondral lesions: Indicators of clinical outcomes.

PURPOSE: To evaluate the utility of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping in evaluation of type II osteochondral lesions (OCLs) of the talus and define cutoff values for identifying patients with good/poor clinical outcomes. MATERIALS AND METHODS: 28 patients (mean age, 42.3 years) underwent T2 mapping and dGEMRIC at least 1.5 years (mean duration, 3.5 years) after microfracture (n = 12) or conservative (n = 16) treatment for type II OCL. Clinical outcomes were considered good with an American Orthopedic Foot and Ankle Society score ≥80. The T1 /T2 -values and indices of repair tissue (RT; cartilage above the OCL) were compared to those of the adjacent normal cartilage (NC) by region-of-interest analysis. The ability of the two methods to discriminate RT from NC was determined by area under the receiver operating characteristics curve (AUC) analysis. The Youden index was maximized for T1 /T2 measures for identifying cutoff values indicative of good/poor clinical outcomes. RESULTS: Repair tissue exhibited lower dGEMRIC values (629.83 vs. 738.51 msec) and higher T2 values (62.07 vs. 40.69 msec) than NC (P < 0.001). T2 mapping exhibited greater AUC than dGEMRIC (0.88 vs. 0.69; P = 0.0398). All T1 measures exhibited higher maximized Youden indices than the corresponding T2 measures. The highest maximized Youden index for T1difference was observed at a cutoff value of 84 msec (sensitivity, 78%; specificity, 83%). CONCLUSION: While T2 mapping is superior to dGEMRIC in discriminating RT, the latter better identifies good/poor clinical outcomes in patients with type II talar OCL. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1601-1610.