Ken Herrmann

18F-FDG PET/MRI in patients suffering from lymphoma: how much MRI information is really needed?

ObjectivesTo evaluate and compare the diagnostic potential of different reading protocols, entailing non-enhanced/contrast-enhanced and diffusion-weighted 18F-FDG PET/MR imaging for lesion detection and determination of the tumor stage in lymphoma patients.MethodsA total of 101 18F-FDG PET/MRI datasets including a (1) transverse T2-w HASTE and 18F-FDG PET (PET/MRI1), (2) with an additional contrast enhanced VIBE (PET/MRI2), and (3) with additional diffusion-weighted imaging (PET/MRI3) were evaluated. Scans were performed for initial staging, restaging during treatment, or at the end of treatment and under surveillance with suspicion for tumor relapse. In all datasets lymphoma manifestations as well as tumor stage in analogy to the revised criteria of the Ann Arbor staging system were determined. Furthermore, potential changes in therapy compared to the reference standard were evaluated. Hitherto performed PET/CT and all available follow-up and prior examinations as well as histopathology served as reference standard.ResultsPET/MRI1 correctly identified 53/55 patients with active lymphoma and 190/205 lesions. Respective values were 55/55, 202/205 for PET/MRI2 and 55/55, 205/205 for PET/MRI3. PET/MRI1 determined correct tumor stage in 88 out of 101 examinations, and corresponding results for PET/MRI2 were 95 out of 101 and 96 out of 101 in PET/MRI3. Relating to the reference standard changes in treatment would occur in 11% based on PET/MRI1, in 6% based on PET/MRI2, and in 3% based on PET/MRI3.ConclusionsThe additional application of contrast-enhanced and diffusion-weighted imaging to 18F-FDG PET/MRI resulted in higher diagnostic competence, particularly for initial staging and correct classification of the disease extent with potential impact on patient and therapy management.

Imaging children suffering from lymphoma: an evaluation of different 18F-FDG PET/MRI protocols compared to whole-body DW-MRI

ObjectivesThe objectives of this study were to evaluate and compare the diagnostic potential of different PET/MRI reading protocols, entailing non-enhanced / contrast-enhanced and diffusion-weighted 18F–FDG PET/MR imaging and whole-body diffusion-weighted MRI for lesion detection and determination of the tumor stage in pediatric lymphoma patients.MethodsA total of 28 18F–FDG PET/MRI datasets were included for analysis of four different reading protocols: (1) PET/MRI utilizing sole unenhanced T2w and T1w imaging, (2) PET/MRI utilizing additional contrast enhanced sequences, (3) PET/MR imaging utilizing unenhanced, contrast enhanced and DW imaging or (4) WB-DW-MRI. Statistical analyses were performed on a per-patient and a per-lesion basis. Follow-up and prior examinations as well as histopathology served as reference standards.ResultsPET/MRI correctly identified all 17 examinations with active lymphoma disease, while WB-DW-MRI correctly identified 15/17 examinations. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 96%, 96.5%, 97%, 95%, and 96% for PET/MRI1; 97%, 96.5%, 97%, 96.5%, and 97% for PET/MRI2; 97%, 96.5%, 97%, 96.5%, and 97% for PET/MRI3 and 77%, 96%, 96%, 78.5% and 86% for MRI-DWI.Conclusion18F–FDG PET/MRI is superior to WB-DW-MRI in staging pediatric lymphoma patients. Neither application of contrast media nor DWI leads to a noticeable improvement of the diagnostic accuracy of PET/MRI. Thus, unenhanced PET/MRI may play a crucial role for the diagnostic work-up of pediatric lymphoma patients in the future.

Dual-phase hybrid 18F-Fluoride Positron emission tomography/MRI in ankylosing spondylitis: Investigating the link between MRI bone changes, regional hyperaemia and increased osteoblastic activity

Focal 18F‐Fluoride uptake on blood‐pool phase PET represents regional hyperaemia, while it indicates osteoblastic activity on mineralization phase PET. This study investigates the link between regional hyperaemia and osteoblastic activity in inflammatory and chronic lesions of ankylosing spondylitis (AS) of the sacroiliac joints (SIJ) using dual‐phase 18F‐Fluoride PET/MRI.

11C–MET PET/MRI for detection of recurrent glioma

IntroductionRadiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid 11C–MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma.MethodsFifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid 11C–MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid 11C–MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis.ResultsHybrid 11C–MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for 11C–MET PET (96.77% and 73.68%), and for hybrid 11C–MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid 11C–MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C–MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing 11C–MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733).ConclusionThis feasibility study showed that hybrid PET/MRI might strengthen RANO classification by adding metabolic information to conventional MRI information. Future studies should evaluate the clinical utility of the combined use of 11C–MET PET/MRI in larger patient cohorts.

Simultaneous multiparametric PET/MRI for the assessment of therapeutic response to chemotherapy or concurrent chemoradiotherapy of cervical cancer patients: Preliminary results

PURPOSE To assess the response to initial treatment strategies of cervical cancer using multiparametric-PET/MRI. MATERIAL AND METHODS PET/MR-derived morphological (tumor size), functional (DWI, DCE-MRI) and metabolic (18F-FDG PET) parameters were acquired in pre- and posttreatment examinations of 8 patients. Besides RECIST- and PERCIST-criteria, functional quantitative parameters were used to assess therapeutic response. RESULTS RECIST- and PERCIST-response criteria demonstrated high correlations for the differentiation between therapy-responders and non-responders, which was additionally reflected by functional (DWI, DCE-MRI) quantitative imaging parameters. CONCLUSION Multiparametric-PET/MRI bears the potential of a more comprehensive response assessment of initial treatment strategies in cervical cancer patients.

Current and Emerging Applications

Integrated PET/MRI systems have been successfully introduced into scientific and clinical applications within the past 7 years, leveraging hybrid imaging onto a new platform of simultaneous acquisition of complementary metabolic, functional and morphologic information based on simultaneously obtained PET and MR data sets. While the integration of PET systems into whole-body MR scanners was a challenging task to overcome demanding a great amount of technological and methodological adjustments and modifications, the interchange of the CT component with MRI has been proven well worth the defying work. The unparalleled soft-tissue contrast of MRI, exact co-registration of PET and MR data and the inherent multifunctionality of MRI, in terms of the potential for multiparametric MR imaging and associated acquisition of non-invasive tissue features and biomarkers, are only some of the benefits to be named. While the transition of PET/MRI from exclusive scientific applications to clinical viability has been well demonstrated, it remains to be the source of continuous and on-going research on clinical, methodological and technical issues.

MET Expression in Advanced Non–Small-Cell Lung Cancer: Effect on Clinical Outcomes of Chemotherapy, Targeted Therapy, and Immunotherapy

&NA; We studied the effect of MET expression in a prospectively recruited cohort of patients (n = 384) with advanced non–small‐cell lung cancer (NSCLC). High MET expression was associated with inferior outcome of epidermal growth factor receptor‐targeting therapy, but with a more favorable outcome with programmed death 1/programmed death ligand 1‐directed therapy. MET mutations were detected at low prevalence (0.78%) and MET‐mutated NSCLC appeared—on an anecdotal basis—to respond less to immunotherapy. Background: The receptor tyrosine kinase MET is implicated in malignant transformation, tumor progression, metastasis, and acquired treatment resistance. We conducted an analysis of the effect of MET expression and MET genomic aberrations on the outcome of patients with advanced or metastatic pulmonary adenocarcinomas prospectively enrolled in an institutional precision oncology program. Patients and Methods: Standardized immunohistochemistry (IHC) analyses of MET and markers of pathway activation were available in 384 patients, and next‐generation sequencing‐based MET hotspot mutation analyses were available from 892 patients. Clinical data were retrieved with a median follow‐up from initial diagnosis of 37 months. Results: High MET expression, defined as MET IHC 3+ or MET H‐Score in the upper quartile, was observed in 102 of 384 patients (26.6%). MET exon 14 mutations were only detected in 7 of 892 patients (0.78%). High MET expression correlated with activation markers of the mitogen‐activated protein kinase (MAPK) and phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT) pathways only in cases without Kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), v‐Raf murine sarcoma viral oncogene homolog B (BRAF), anaplastic lymphoma kinase (ALK) and proto‐oncogene tyrosine‐protein kinase ROS (ROS1) aberrations. There was no association of MET expression with outcome during chemotherapy. High MET expression negatively affected the outcome during EGFR‐targeting therapy but was associated with more favorable results with programmed death 1/programmed death ligand 1 (PD‐L1)‐directed therapy, independent of smoking history, PD‐L1 expression or KRAS mutation. Two patients with MET exon 14 mutation and high PD‐L1 expression failed to respond to pembrolizumab. Conclusion: MET expression affects the outcomes of targeted therapies in non–small‐cell lung cancer, thus supporting the development of biomarker‐informed combination strategies. The interaction of MET expression and MET mutation with immune checkpoint inhibitor therapy is novel and merits further investigation.

18F-FDG PET/CT may exclude malignancy in sonographically suspicious and scintigraphically hypofunctional thyroid nodules and reduce unnecessary thyroid surgeries

BACKGROUND The aim of this study was to evaluate whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful in the further characterization of sonographically suspicious and scintigraphically hypofunctional thyroid nodules. METHODS Sixty-five patients with sonographically suspicious thyroid nodules that were hypofunctional on 99m-Tc-pertechnetate scintigraphy (diameter >1 cm) were retrospectively analyzed. All patients underwent evaluation with FDG-PET/CT. Thyroid nodules were sonographically categorized by Thyroid Image Reporting and Data System (TIRADS) criteria. FDG uptake in the thyroid nodules was visually compared to the remainder of the thyroid tissue and categorized as pathological or non-pathological. In cases of pathologically increased uptake, maximum standardized uptake values (SUVmax) of the suspicious nodule and the perinodular thyroid tissue were determined. Depending on the results of the FDG-PET/CT, patients underwent thyroid surgery (pathological FDG uptake) or follow-up examinations (non-pathological FDG uptake). The endpoints for comparison with the FDG uptake were either histological results or sonographic follow-up examinations of at least five years. RESULTS In 18/65 (28%) patients, PET/CT showed visually pathological FDG uptake in the suspicious thyroid nodules (SUVmax 7.1 ± 4.6). Of these nodules, 3/18 (17%) were sonographically categorized as TIRADS 4a, 11/18 (61%) nodules as TIRADS 4b, 3/18 (17%) nodules as TIRADS 4c, and 1/18 (6%) nodule as TIRADS 5. The other nodules without pathological FDG uptake were categorized as TIRADS 4a in 24/47 (51%) patients, as TIRADS 4b in 18/47 (38%), and as TIRADS 4c in 5/47 (11%) patients. Twenty-three patients (18 FDG positive, 5 FDG negative) underwent surgery. The other patients underwent follow-up examinations with stability on observation over at least five years as a surrogate endpoint. Taking into consideration that FDG-PET/CT was rated as true negative in 42/47 patients with stability on sonographic follow-up, sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET/CT in detecting malignancy in the suspicious thyroid nodules were 100%, 87%, 61%, and 100%, respectively. CONCLUSION FDG-PET/CT allows stratification of patients with sonographically suspicious and scintigraphically hypofunctional thyroid nodules with a positive predictive value of 61% and negative predictive value of 100%. The absence of visually pathological FDG uptake in suspicious thyroid nodules may be useful for avoiding unnecessary thyroid surgery.Background: The aim of this study was to evaluate whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful in the further characterization of sonographically suspicious and scintigraphically hypofunctional thyroid nodules. Methods: Sixty-five patients with sonographically suspicious thyroid nodules that were hypofunctional on 99m-Tc-pertechnetate scintigraphy (diameter >1 cm) were retrospectively analyzed. All patients underwent evaluation with FDG-PET/CT. Thyroid nodules were sonographically categorized by Thyroid Image Reporting and Data System (TIRADS) criteria. FDG uptake in the thyroid nodules was visually compared to the remainder of the thyroid tissue and categorized as pathological or non-pathological. In cases of pathologically increased uptake, maximum standardized uptake values (SUVmax) of the suspicious nodule and the perinodular thyroid tissue were determined. Depending on the results of the FDG-PET/CT, patients underwent thyroid surgery (patholog...